rs4628676

Variant names:

• chr11-68714762-A-G
• rs4628676
• NM_004923.3:c.1020+1075T>C

Variant summary

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

The NM_004923.3(TESMIN):​c.1020+1075T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 152,082 control chromosomes in the GnomAD database, including 29,162 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 0.61 (29162 hom., cov: 32)
• Consequence: TESMIN NM_004923.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.39
• Publications: 3 publications found

Genes affected

TESMIN (HGNC:7446): (testis expressed metallothionein like protein) Metallothionein proteins are highly conserved low-molecular-weight cysteine-rich proteins that are induced by and bind to heavy metal ions and have no enzymatic activity. They may play a central role in the regulation of cell growth and differentiation and are involved in spermatogenesis. This gene encodes a metallothionein-like protein which has been shown to be expressed differentially in mouse testis and ovary. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TESMIN	NM_004923.3	c.1020+1075T>C		intron_variant	Intron 7 of 9	ENST00000255087.10	NP_004914.2
TESMIN	XM_011545402.2	c.1020+1075T>C		intron_variant	Intron 7 of 10		XP_011543704.1
TESMIN	XM_017018588.2	c.822+1075T>C		intron_variant	Intron 5 of 8		XP_016874077.1
TESMIN	XM_047427921.1	c.822+1075T>C		intron_variant	Intron 5 of 8		XP_047283877.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TESMIN	ENST00000255087.10	c.1020+1075T>C		intron_variant	Intron 7 of 9	1	NM_004923.3	ENSP00000255087.5
TESMIN	ENST00000543240.1	c.96+1075T>C		intron_variant	Intron 1 of 4	3		ENSP00000454311.1

Frequencies

GnomAD3 genomes AF: 0.607 AC: 92248 AN: 151964 Hom.: 29156 Cov.: 32

Gnomad AFR AF: 0.441

Gnomad AMI AF: 0.538

Gnomad AMR AF: 0.655

Gnomad ASJ AF: 0.685

Gnomad EAS AF: 0.782

Gnomad SAS AF: 0.653

Gnomad FIN AF: 0.855

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.640

Gnomad OTH AF: 0.597

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

GnomAD4 genome AF: 0.607 AC: 92283 AN: 152082 Hom.: 29162 Cov.: 32 AF XY: 0.619 AC XY: 46053 AN XY: 74344

African (AFR) AF: 0.441 AC: 18267 AN: 41448

American (AMR) AF: 0.655 AC: 10025 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.685 AC: 2378 AN: 3470

East Asian (EAS) AF: 0.781 AC: 4039 AN: 5170

South Asian (SAS) AF: 0.652 AC: 3141 AN: 4816

European-Finnish (FIN) AF: 0.855 AC: 9052 AN: 10582

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.640 AC: 43481 AN: 67982

Other (OTH) AF: 0.599 AC: 1266 AN: 2112

Alfa AF: 0.602 Hom.: 5524

Bravo AF: 0.581

Asia WGS AF: 0.706 AC: 2454 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.031
DANN	Benign	0.22
PhyloP100		-2.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs4628676; hg19: chr11-68482230;