1-58576268-T-C

Position:

• chr1-58576268-T-C

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.889A>G​(p.Ile297Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00537 in 1,613,902 control chromosomes in the GnomAD database, including 350 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.027 (188 hom., cov: 33)
  • Exomes 𝑓: 0.0031 (162 hom.)
• Consequence: TACSTD2 NM_002353.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0950

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 (MetaRNN=0.0015203059).
• BP6: Variant 1-58576268-T-C is Benign according to our data. Variant chr1-58576268-T-C is described in ClinVar as [Benign]. Clinvar id is 297764.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0894 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TACSTD2	NM_002353.3	c.889A>G	p.Ile297Val	missense_variant	1/1	ENST00000371225.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TACSTD2	ENST00000371225.4	c.889A>G	p.Ile297Val	missense_variant	1/1		NM_002353.3	P1

Frequencies

GnomAD3 genomes AF: 0.0268 AC: 4071 AN: 152144 Hom.: 186 Cov.: 33

Gnomad AFR AF: 0.0917

Gnomad AMI AF: 0.0297

Gnomad AMR AF: 0.00962

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000720

Gnomad OTH AF: 0.0229

GnomAD3 exomes AF: 0.00704 AC: 1760 AN: 250008 Hom.: 56 AF XY: 0.00528 AC XY: 714 AN XY: 135196

Gnomad AFR exome AF: 0.0902

Gnomad AMR exome AF: 0.00528

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000545

Gnomad SAS exome AF: 0.000328

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000841

Gnomad OTH exome AF: 0.00442

GnomAD4 exome AF: 0.00314 AC: 4584 AN: 1461640 Hom.: 162 Cov.: 31 AF XY: 0.00273 AC XY: 1985 AN XY: 727110

Gnomad4 AFR exome AF: 0.0943

Gnomad4 AMR exome AF: 0.00599

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000278

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000567

Gnomad4 OTH exome AF: 0.00762

GnomAD4 genome AF: 0.0268 AC: 4087 AN: 152262 Hom.: 188 Cov.: 33 AF XY: 0.0257 AC XY: 1916 AN XY: 74450

Gnomad4 AFR AF: 0.0918

Gnomad4 AMR AF: 0.00954

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000706

Gnomad4 OTH AF: 0.0227

Alfa AF: 0.00397 Hom.: 38

Bravo AF: 0.0307

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.0903 AC: 398

ESP6500EA AF: 0.000698 AC: 6

ExAC AF: 0.00838 AC: 1017

Asia WGS AF: 0.00751 AC: 26 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.00101

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Lattice corneal dystrophy Type III 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. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 12, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	6.9
DANN	Benign	0.80
DEOGEN2	Benign	0.068	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.058	N
LIST_S2	Benign	0.61	T
MetaRNN	Benign	0.0015	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.13
Sift	Benign	0.49	T
Sift4G	Benign	0.85	T
Polyphen		0.0010	B
Vest4		0.071
MVP		0.69
MPC		0.37
ClinPred		0.0014	T
GERP RS		0.99
Varity_R		0.051
gMVP		0.25

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: rs114373153; hg19: chr1-59041940;