rs2273001

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 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/exons	MANE	UniProt
TULP1	NM_003322.6	c.499+26C>T		intron_variant		ENST00000229771.11
TULP1	NM_001289395.2	c.340+26C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TULP1	ENST00000229771.11	c.499+26C>T		intron_variant		1	NM_003322.6	P4

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

GnomAD3 exomes AF: 0.689 AC: 172626 AN: 250402 Hom.: 59896 AF XY: 0.696 AC XY: 94271 AN XY: 135458

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 SAS exome AF: 0.703

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

Gnomad4 AFR exome AF: 0.525

Gnomad4 AMR exome AF: 0.654

Gnomad4 ASJ exome AF: 0.719

Gnomad4 EAS exome AF: 0.729

Gnomad4 SAS exome AF: 0.705

Gnomad4 FIN exome AF: 0.738

Gnomad4 NFE exome AF: 0.701

Gnomad4 OTH exome AF: 0.689

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

Gnomad4 AFR AF: 0.525

Gnomad4 AMR AF: 0.653

Gnomad4 ASJ AF: 0.727

Gnomad4 EAS AF: 0.730

Gnomad4 SAS AF: 0.693

Gnomad4 FIN AF: 0.748

Gnomad4 NFE AF: 0.705

Gnomad4 OTH AF: 0.648

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

Submissions by phenotype

Retinitis pigmentosa 14 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Leber congenital amaurosis 15 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.5
DANN	Benign	0.59

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

LitVar

Other links and lift over

dbSNP: rs2273001; hg19: chr6-35478612;