6-35512485-T-C

Variant names:

• chr6-35512485-T-C
• rs1540910
• NM_003322.6:c.99+154A>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.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
• Publications: 8 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

ENSG00000228559 (HGNC:58100):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
TULP1	NM_003322.6	c.99+154A>G		intron_variant	Intron 2 of 14	ENST00000229771.11	NP_003313.3
TULP1	NM_001289395.2	c.99+154A>G		intron_variant	Intron 2 of 13		NP_001276324.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TULP1	ENST00000229771.11	c.99+154A>G		intron_variant	Intron 2 of 14	1	NM_003322.6	ENSP00000229771.6

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

African (AFR) AF: 0.825 AC: 34021 AN: 41246

American (AMR) AF: 0.730 AC: 11119 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.739 AC: 2563 AN: 3470

East Asian (EAS) AF: 0.759 AC: 3830 AN: 5048

South Asian (SAS) AF: 0.661 AC: 3166 AN: 4788

European-Finnish (FIN) AF: 0.764 AC: 8039 AN: 10526

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.740 AC: 50124 AN: 67758

Other (OTH) AF: 0.743 AC: 1560 AN: 2100

Alfa AF: 0.743 Hom.: 54626

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

Mar 03, 2015

GeneDx

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	-0.88
CADD	Benign	0.50
DANN	Benign	0.46
PhyloP100		-1.0
PromoterAI		0.0063	Neutral
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

Other links and lift over

dbSNP: rs1540910; hg19: chr6-35480262;