rs11068315

Variant names:

• chr12-117072747-C-T
• rs11068315
• NM_017899.4:c.128+2524G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017899.4(TESC):​c.128+2524G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0541 in 152,246 control chromosomes in the GnomAD database, including 340 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.054 (340 hom., cov: 32)
• Consequence: TESC NM_017899.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45
• Publications: 3 publications found

Genes affected

TESC (HGNC:26065): (tescalcin) Enables calcium ion binding activity. Involved in several processes, including cellular response to retinoic acid; positive regulation of macromolecule metabolic process; and positive regulation of myeloid cell differentiation. Located in several cellular components, including cytosol; lamellipodium; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TESC	NM_017899.4	c.128+2524G>A		intron_variant	Intron 2 of 7	ENST00000335209.12	NP_060369.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TESC	ENST00000335209.12	c.128+2524G>A		intron_variant	Intron 2 of 7	1	NM_017899.4	ENSP00000334785.7

Frequencies

GnomAD3 genomes AF: 0.0542 AC: 8239 AN: 152128 Hom.: 340 Cov.: 32

Gnomad AFR AF: 0.0113

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0456

Gnomad ASJ AF: 0.0556

Gnomad EAS AF: 0.000965

Gnomad SAS AF: 0.0209

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0773

Gnomad OTH AF: 0.0411

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

GnomAD4 genome AF: 0.0541 AC: 8239 AN: 152246 Hom.: 340 Cov.: 32 AF XY: 0.0550 AC XY: 4090 AN XY: 74428

African (AFR) AF: 0.0112 AC: 467 AN: 41558

American (AMR) AF: 0.0455 AC: 696 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0556 AC: 193 AN: 3470

East Asian (EAS) AF: 0.000967 AC: 5 AN: 5172

South Asian (SAS) AF: 0.0214 AC: 103 AN: 4820

European-Finnish (FIN) AF: 0.131 AC: 1384 AN: 10592

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0773 AC: 5256 AN: 68020

Other (OTH) AF: 0.0407 AC: 86 AN: 2114

Alfa AF: 0.0635 Hom.: 686

Bravo AF: 0.0435

Asia WGS AF: 0.0120 AC: 43 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.32
DANN	Benign	0.57
PhyloP100		-1.5
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: rs11068315; hg19: chr12-117510552;