chr6-35498009-A-C

Variant names:

• chr6-35498009-A-C
• rs1051952
• NM_003322.6:c.*318T>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003322.6(TULP1):​c.*318T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 515,366 control chromosomes in the GnomAD database, including 71,170 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.58 (28177 hom., cov: 31)
  • Exomes 𝑓: 0.48 (42993 hom.)
• Consequence: TULP1 NM_003322.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.216
• Publications: 23 publications found

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: Labcorp Genetics (formerly Invitae), G2P
• 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

LINC03135 (HGNC:58100):

LOC124901309 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 6-35498009-A-C is Benign according to our data. Variant chr6-35498009-A-C is described in ClinVar as Benign. ClinVar VariationId is 356460.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003322.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TULP1	NM_003322.6	MANE Select	c.*318T>G		3_prime_UTR	Exon 15 of 15	NP_003313.3
	TULP1	NM_001289395.2		c.*318T>G		3_prime_UTR	Exon 14 of 14	NP_001276324.1	O00294-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TULP1	ENST00000229771.11	TSL:1 MANE Select	c.*318T>G		3_prime_UTR	Exon 15 of 15	ENSP00000229771.6	O00294-1
	TULP1	ENST00000322263.8	TSL:1	c.*318T>G		3_prime_UTR	Exon 14 of 14	ENSP00000319414.4	O00294-2
	TULP1	ENST00000614066.4	TSL:5	c.*318T>G		3_prime_UTR	Exon 14 of 14	ENSP00000477534.1	A0A087WT25

Frequencies

GnomAD3 genomes AF: 0.580 AC: 87899 AN: 151456 Hom.: 28127 Cov.: 31

Gnomad AFR AF: 0.869

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.421

Gnomad EAS AF: 0.588

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.426

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.517

GnomAD4 exome AF: 0.477 AC: 173485 AN: 363794 Hom.: 42993 Cov.: 3 AF XY: 0.475 AC XY: 90121 AN XY: 189790

African (AFR) AF: 0.864 AC: 9332 AN: 10800

American (AMR) AF: 0.488 AC: 7706 AN: 15788

Ashkenazi Jewish (ASJ) AF: 0.402 AC: 4632 AN: 11526

East Asian (EAS) AF: 0.540 AC: 12993 AN: 24046

South Asian (SAS) AF: 0.492 AC: 19491 AN: 39628

European-Finnish (FIN) AF: 0.422 AC: 9625 AN: 22804

Middle Eastern (MID) AF: 0.361 AC: 579 AN: 1602

European-Non Finnish (NFE) AF: 0.456 AC: 98612 AN: 216338

Other (OTH) AF: 0.495 AC: 10515 AN: 21262

GnomAD4 genome AF: 0.581 AC: 88010 AN: 151572 Hom.: 28177 Cov.: 31 AF XY: 0.577 AC XY: 42751 AN XY: 74068

African (AFR) AF: 0.870 AC: 36093 AN: 41500

American (AMR) AF: 0.514 AC: 7843 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.421 AC: 1454 AN: 3454

East Asian (EAS) AF: 0.587 AC: 2995 AN: 5098

South Asian (SAS) AF: 0.507 AC: 2430 AN: 4796

European-Finnish (FIN) AF: 0.426 AC: 4462 AN: 10484

Middle Eastern (MID) AF: 0.378 AC: 108 AN: 286

European-Non Finnish (NFE) AF: 0.459 AC: 31080 AN: 67718

Other (OTH) AF: 0.519 AC: 1088 AN: 2098

Alfa AF: 0.484 Hom.: 28730

Bravo AF: 0.598

Asia WGS AF: 0.550 AC: 1913 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Leber congenital amaurosis 15 (1)
-	-	1	Retinitis pigmentosa (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	18
DANN	Benign	0.75
PhyloP100		0.22
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1051952; hg19: chr6-35465786;