rs4628676

chr11-68714762-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
TESMIN	NM_004923.3	c.1020+1075T>C		intron_variant		ENST00000255087.10
TESMIN	XM_011545402.2	c.1020+1075T>C		intron_variant
TESMIN	XM_017018588.2	c.822+1075T>C		intron_variant
TESMIN	XM_047427921.1	c.822+1075T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TESMIN	ENST00000255087.10	c.1020+1075T>C		intron_variant		1	NM_004923.3	P1
TESMIN	ENST00000543240.1	c.98+1075T>C		intron_variant		3

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

Gnomad4 AFR AF: 0.441

Gnomad4 AMR AF: 0.655

Gnomad4 ASJ AF: 0.685

Gnomad4 EAS AF: 0.781

Gnomad4 SAS AF: 0.652

Gnomad4 FIN AF: 0.855

Gnomad4 NFE AF: 0.640

Gnomad4 OTH AF: 0.599

Alfa AF: 0.607 Hom.: 5454

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs4628676; hg19: chr11-68482230;