chr6-35510835-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003322.6(TULP1):c.499+26C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.693 in 1,612,748 control chromosomes in the GnomAD database, including 389,180 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.65 ( 33011 hom., cov: 31)

Exomes 𝑓: 0.70 ( 356169 hom. )

Consequence

TULP1
NM_003322.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.879

Publications

13 publications found

Variant links:

Genes affected

TULP1 (HGNC:12423): (TUB like protein 1) This gene encodes a member of the tubby-like gene family (TULPs). Members of this family have been identified in plants, vertebrates, and invertebrates. TULP proteins share a conserved C-terminal region of approximately 200 amino acid residues. The protein encoded by this gene is thought to play a role in the physiology of photoreceptors. Mutations in this gene are associated with recessive juvenile retinitis pigmentosa and Leber congenital amaurosis-15. [provided by RefSeq, Nov 2016]

TULP1 Gene-Disease associations (from GenCC):

retinitis pigmentosa 14
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
Leber congenital amaurosis 15
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
Leber congenital amaurosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
retinitis pigmentosa
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

TULP1 links:

ENSG00000228559 (HGNC:58100):

ENSG00000228559 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 6-35510835-G-A is Benign according to our data. Variant chr6-35510835-G-A is described in CliVar as Benign. Clinvar id is 1290548.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-35510835-G-A is described in CliVar as Benign. Clinvar id is 1290548.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-35510835-G-A is described in CliVar as Benign. Clinvar id is 1290548.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-35510835-G-A is described in CliVar as Benign. Clinvar id is 1290548.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-35510835-G-A is described in CliVar as Benign. Clinvar id is 1290548.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-35510835-G-A is described in CliVar as Benign. Clinvar id is 1290548.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TULP1	NM_003322.6 link	c.499+26C>T		intron_variant	Intron 5 of 14	ENST00000229771.11	NP_003313.3	O00294-1Q0QD38
TULP1	NM_001289395.2 link	c.340+26C>T		intron_variant	Intron 4 of 13		NP_001276324.1	O00294-2F1T0I9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TULP1	ENST00000229771.11 link	c.499+26C>T		intron_variant	Intron 5 of 14	1	NM_003322.6	ENSP00000229771.6		O00294-1

Frequencies

GnomAD3 genomes

AF:

0.654

AC:

99398

AN:

151910

Hom.:

32994

Cov.:

show subpopulations

Gnomad AFR

AF:

0.525

Gnomad AMI

AF:

0.827

Gnomad AMR

AF:

0.653

Gnomad ASJ

AF:

0.727

Gnomad EAS

AF:

0.729

Gnomad SAS

AF:

0.692

Gnomad FIN

AF:

0.748

Gnomad MID

AF:

0.636

Gnomad NFE

AF:

0.705

Gnomad OTH

AF:

0.647

GnomAD2 exomes

AF:

0.689

AC:

172626

AN:

250402

AF XY:

0.696

show subpopulations

Gnomad AFR exome

AF:

0.522

Gnomad AMR exome

AF:

0.657

Gnomad ASJ exome

AF:

0.713

Gnomad EAS exome

AF:

0.722

Gnomad FIN exome

AF:

0.734

Gnomad NFE exome

AF:

0.703

Gnomad OTH exome

AF:

0.704

GnomAD4 exome

AF:

0.698

AC:

1018945

AN:

1460720

Hom.:

356169

Cov.:

AF XY:

0.698

AC XY:

507540

AN XY:

726720

show subpopulations

African (AFR)

AF:

0.525

AC:

17562

AN:

33478

American (AMR)

AF:

0.654

AC:

29257

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.719

AC:

18798

AN:

26136

East Asian (EAS)

AF:

0.729

AC:

28952

AN:

39696

South Asian (SAS)

AF:

0.705

AC:

60838

AN:

86258

European-Finnish (FIN)

AF:

0.738

AC:

38581

AN:

52306

Middle Eastern (MID)

AF:

0.675

AC:

3892

AN:

5768

European-Non Finnish (NFE)

AF:

0.701

AC:

779450

AN:

1111970

Other (OTH)

AF:

0.689

AC:

41615

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

19036

38071

57107

76142

95178

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19668

39336

59004

78672

98340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.654

AC:

99452

AN:

152028

Hom.:

33011

Cov.:

AF XY:

0.659

AC XY:

48949

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.525

AC:

21760

AN:

41478

American (AMR)

AF:

0.653

AC:

9972

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.727

AC:

2524

AN:

3472

East Asian (EAS)

AF:

0.730

AC:

3756

AN:

5146

South Asian (SAS)

AF:

0.693

AC:

3336

AN:

4812

European-Finnish (FIN)

AF:

0.748

AC:

7921

AN:

10588

Middle Eastern (MID)

AF:

0.626

AC:

184

AN:

294

European-Non Finnish (NFE)

AF:

0.705

AC:

47879

AN:

67950

Other (OTH)

AF:

0.648

AC:

1367

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

1692

3385

5077

6770

8462

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

806

1612

2418

3224

4030

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.682

Hom.:

6408

Bravo

AF:

0.642

Asia WGS

AF:

0.706

AC:

2454

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Retinitis pigmentosa 14

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Leber congenital amaurosis 15

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

5.5

(source)

DANN

Benign

0.59

PhyloP100

0.88

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over