rs1051952

chr6-35498009-A-Cchr6-35498009-A-Gchr6-35498009-A-T

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.*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

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=-0.63).
• BP6: Variant 6-35498009-A-C is Benign according to our data. Variant chr6-35498009-A-C is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TULP1	NM_003322.6	c.*318T>G		3_prime_UTR_variant	15/15	ENST00000229771.11
TULP1	NM_001289395.2	c.*318T>G		3_prime_UTR_variant	14/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TULP1	ENST00000229771.11	c.*318T>G		3_prime_UTR_variant	15/15	1	NM_003322.6	P4
TULP1	ENST00000322263.8	c.*318T>G		3_prime_UTR_variant	14/14	1		A2
TULP1	ENST00000614066.4	c.*318T>G		3_prime_UTR_variant	14/14	5		A2

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

Gnomad4 AFR exome AF: 0.864

Gnomad4 AMR exome AF: 0.488

Gnomad4 ASJ exome AF: 0.402

Gnomad4 EAS exome AF: 0.540

Gnomad4 SAS exome AF: 0.492

Gnomad4 FIN exome AF: 0.422

Gnomad4 NFE exome AF: 0.456

Gnomad4 OTH exome AF: 0.495

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

Gnomad4 AFR AF: 0.870

Gnomad4 AMR AF: 0.514

Gnomad4 ASJ AF: 0.421

Gnomad4 EAS AF: 0.587

Gnomad4 SAS AF: 0.507

Gnomad4 FIN AF: 0.426

Gnomad4 NFE AF: 0.459

Gnomad4 OTH AF: 0.519

Alfa AF: 0.474 Hom.: 18663

Bravo AF: 0.598

Asia WGS AF: 0.550 AC: 1913 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Leber congenital amaurosis 15 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Retinitis pigmentosa Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
Cadd	Benign	18
Dann	Benign	0.75

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: rs1051952; hg19: chr6-35465786;