rs2273001

Variant names:

• chr6-35510835-G-A
• rs2273001
• NM_003322.6:c.499+26C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-35510835-G-A
• chr6-35510835-G-C
• chr6-35510835-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.879
• Publications: 13 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: 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

LINC03135 (HGNC:58100):

ACMG classification

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 ClinVar as Benign. ClinVar VariationId 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.

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.499+26C>T		intron	N/A	NP_003313.3
	TULP1	NM_001289395.2		c.340+26C>T		intron	N/A	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.499+26C>T		intron	N/A	ENSP00000229771.6	O00294-1
	TULP1	ENST00000322263.8	TSL:1	c.340+26C>T		intron	N/A	ENSP00000319414.4	O00294-2
	TULP1	ENST00000614066.4	TSL:5	c.499+26C>T		intron	N/A	ENSP00000477534.1	A0A087WT25

Frequencies

GnomAD3 genomes AF: 0.654 AC: 99398 AN: 151910 Hom.: 32994 Cov.: 31

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

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.: 76 AF XY: 0.698 AC XY: 507540 AN XY: 726720

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

GnomAD4 genome AF: 0.654 AC: 99452 AN: 152028 Hom.: 33011 Cov.: 31 AF XY: 0.659 AC XY: 48949 AN XY: 74320

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

Alfa AF: 0.682 Hom.: 6408

Bravo AF: 0.642

Asia WGS AF: 0.706 AC: 2454 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Leber congenital amaurosis 15 (1)
-	-	1	not provided (1)
-	-	1	Retinitis pigmentosa 14 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.5
DANN	Benign	0.59
PhyloP100		0.88
Mutation Taster		=100/0	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2273001;

hg19: chr6-35478612;

COSMIC: COSV107214694;

COSMIC: COSV107214694;