1-58576137-C-T

Variant names:

• chr1-58576137-C-T
• rs41311174
• NM_002353.3:c.*48G>A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002353.3(TACSTD2):​c.*48G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0879 in 1,596,804 control chromosomes in the GnomAD database, including 6,675 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.077 (489 hom., cov: 33)
  • Exomes 𝑓: 0.089 (6186 hom.)
• Consequence: TACSTD2 NM_002353.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.525

Genes affected

TACSTD2 (HGNC:11530): (tumor associated calcium signal transducer 2) This intronless gene encodes a carcinoma-associated antigen. This antigen is a cell surface receptor that transduces calcium signals. Mutations of this gene have been associated with gelatinous drop-like corneal dystrophy.[provided by RefSeq, Dec 2009]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 1-58576137-C-T is Benign according to our data. Variant chr1-58576137-C-T is described in ClinVar as [Benign]. Clinvar id is 297763.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0963 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TACSTD2	NM_002353.3	c.*48G>A		3_prime_UTR_variant	Exon 1 of 1	ENST00000371225.4	NP_002344.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TACSTD2	ENST00000371225	c.*48G>A		3_prime_UTR_variant	Exon 1 of 1		NM_002353.3	ENSP00000360269.2

Frequencies

GnomAD3 genomes AF: 0.0774 AC: 11779 AN: 152176 Hom.: 488 Cov.: 33

Gnomad AFR AF: 0.0519

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.0730

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.00250

Gnomad SAS AF: 0.0574

Gnomad FIN AF: 0.0783

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.0983

Gnomad OTH AF: 0.0908

GnomAD3 exomes AF: 0.0761 AC: 17051 AN: 224032 Hom.: 732 AF XY: 0.0785 AC XY: 9472 AN XY: 120604

Gnomad AFR exome AF: 0.0528

Gnomad AMR exome AF: 0.0514

Gnomad ASJ exome AF: 0.101

Gnomad EAS exome AF: 0.00165

Gnomad SAS exome AF: 0.0626

Gnomad FIN exome AF: 0.0819

Gnomad NFE exome AF: 0.0990

Gnomad OTH exome AF: 0.0938

GnomAD4 exome AF: 0.0890 AC: 128589 AN: 1444510 Hom.: 6186 Cov.: 30 AF XY: 0.0893 AC XY: 64056 AN XY: 717338

Gnomad4 AFR exome AF: 0.0543

Gnomad4 AMR exome AF: 0.0532

Gnomad4 ASJ exome AF: 0.0996

Gnomad4 EAS exome AF: 0.000906

Gnomad4 SAS exome AF: 0.0631

Gnomad4 FIN exome AF: 0.0777

Gnomad4 NFE exome AF: 0.0966

Gnomad4 OTH exome AF: 0.0887

GnomAD4 genome AF: 0.0774 AC: 11788 AN: 152294 Hom.: 489 Cov.: 33 AF XY: 0.0752 AC XY: 5601 AN XY: 74460

Gnomad4 AFR AF: 0.0519

Gnomad4 AMR AF: 0.0729

Gnomad4 ASJ AF: 0.100

Gnomad4 EAS AF: 0.00251

Gnomad4 SAS AF: 0.0585

Gnomad4 FIN AF: 0.0783

Gnomad4 NFE AF: 0.0983

Gnomad4 OTH AF: 0.0899

Alfa AF: 0.0922 Hom.: 178

Bravo AF: 0.0756

Asia WGS AF: 0.0420 AC: 147 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Gelatinous droplike corneal dystrophy Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	-0.70
CADD	Benign	4.0
DANN	Benign	0.92

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: rs41311174; hg19: chr1-59041809;