12-117046631-G-A

Variant names:

• chr12-117046631-G-A
• rs76346744
• NM_017899.4:c.447C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_017899.4(TESC):​c.447C>T​(p.Ile149Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 1,551,826 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0050 (7 hom., cov: 33)
  • Exomes 𝑓: 0.00060 (4 hom.)
• Consequence: TESC NM_017899.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.161
• 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 12-117046631-G-A is Benign according to our data. Variant chr12-117046631-G-A is described in ClinVar as Benign. ClinVar VariationId is 787934.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.161 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00498 (758/152320) while in subpopulation AFR AF = 0.0175 (728/41566). AF 95% confidence interval is 0.0165. There are 7 homozygotes in GnomAd4. There are 340 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017899.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TESC	NM_017899.4	MANE Select	c.447C>T	p.Ile149Ile	synonymous	Exon 6 of 8	NP_060369.3	Q96BS2-1
	TESC	NM_001168325.2		c.366C>T	p.Ile122Ile	synonymous	Exon 5 of 7	NP_001161797.1	Q96BS2-3
	TESC	NR_031766.3		n.586C>T		non_coding_transcript_exon	Exon 6 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TESC	ENST00000335209.12	TSL:1 MANE Select	c.447C>T	p.Ile149Ile	synonymous	Exon 6 of 8	ENSP00000334785.7	Q96BS2-1
	TESC	ENST00000940881.1		c.447C>T	p.Ile149Ile	synonymous	Exon 6 of 8	ENSP00000610940.1
	TESC	ENST00000874651.1		c.447C>T	p.Ile149Ile	synonymous	Exon 6 of 7	ENSP00000544710.1

Frequencies

GnomAD3 genomes AF: 0.00497 AC: 757 AN: 152202 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.0175

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00103 AC: 162 AN: 156646 AF XY: 0.000703

Gnomad AFR exome AF: 0.0160

Gnomad AMR exome AF: 0.000605

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000659

Gnomad OTH exome AF: 0.000226

GnomAD4 exome AF: 0.000595 AC: 833 AN: 1399506 Hom.: 4 Cov.: 32 AF XY: 0.000524 AC XY: 362 AN XY: 690310

African (AFR) AF: 0.0220 AC: 694 AN: 31608

American (AMR) AF: 0.000644 AC: 23 AN: 35740

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25180

East Asian (EAS) AF: 0.00 AC: 0 AN: 35754

South Asian (SAS) AF: 0.0000379 AC: 3 AN: 79248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49150

Middle Eastern (MID) AF: 0.00140 AC: 8 AN: 5698

European-Non Finnish (NFE) AF: 0.0000398 AC: 43 AN: 1079108

Other (OTH) AF: 0.00107 AC: 62 AN: 58020

GnomAD4 genome AF: 0.00498 AC: 758 AN: 152320 Hom.: 7 Cov.: 33 AF XY: 0.00456 AC XY: 340 AN XY: 74484

African (AFR) AF: 0.0175 AC: 728 AN: 41566

American (AMR) AF: 0.00124 AC: 19 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68026

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.00154 Hom.: 1

Bravo AF: 0.00542

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_noAF	Benign	-0.52
CADD	Benign	3.9
DANN	Benign	0.71
PhyloP100		-0.16
PromoterAI		-0.036	Neutral
Mutation Taster		=100/0	polymorphism

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: rs76346744; hg19: chr12-117484436;