6-35512485-T-C

Position:

• chr6-35512485-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003322.6(TULP1):​c.99+154A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.762 in 151,378 control chromosomes in the GnomAD database, including 44,108 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.76 (44108 hom., cov: 27)
• Consequence: TULP1 NM_003322.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.01

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 6-35512485-T-C is Benign according to our data. Variant chr6-35512485-T-C is described in ClinVar as [Benign]. Clinvar id is 1270023.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.817 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TULP1	NM_003322.6	c.99+154A>G		intron_variant		ENST00000229771.11	NP_003313.3
TULP1	NM_001289395.2	c.99+154A>G		intron_variant			NP_001276324.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TULP1	ENST00000229771.11	c.99+154A>G		intron_variant		1	NM_003322.6	ENSP00000229771	P4
TULP1	ENST00000322263.8	c.99+154A>G		intron_variant		1		ENSP00000319414	A2
TULP1	ENST00000428978.1	c.99+154A>G		intron_variant		3		ENSP00000406765
TULP1	ENST00000614066.4	c.99+154A>G		intron_variant		5		ENSP00000477534	A2

Frequencies

GnomAD3 genomes AF: 0.762 AC: 115239 AN: 151258 Hom.: 44063 Cov.: 27

Gnomad AFR AF: 0.825

Gnomad AMI AF: 0.794

Gnomad AMR AF: 0.729

Gnomad ASJ AF: 0.739

Gnomad EAS AF: 0.758

Gnomad SAS AF: 0.661

Gnomad FIN AF: 0.764

Gnomad MID AF: 0.678

Gnomad NFE AF: 0.740

Gnomad OTH AF: 0.742

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.762 AC: 115341 AN: 151378 Hom.: 44108 Cov.: 27 AF XY: 0.762 AC XY: 56307 AN XY: 73910

Gnomad4 AFR AF: 0.825

Gnomad4 AMR AF: 0.730

Gnomad4 ASJ AF: 0.739

Gnomad4 EAS AF: 0.759

Gnomad4 SAS AF: 0.661

Gnomad4 FIN AF: 0.764

Gnomad4 NFE AF: 0.740

Gnomad4 OTH AF: 0.743

Alfa AF: 0.739 Hom.: 41804

Bravo AF: 0.764

Asia WGS AF: 0.735 AC: 2556 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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	-0.88
CADD	Benign	0.50
DANN	Benign	0.46

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: rs1540910; hg19: chr6-35480262;