rs2076085

chr22-37074001-C-Achr22-37074001-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001374504.1(TMPRSS6):c.1442-356G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 151,924 control chromosomes in the GnomAD database, including 26,585 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 0.58 (26585 hom., cov: 31)
• Consequence: TMPRSS6 NM_001374504.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.71

Genes affected

TMPRSS6 (HGNC:16517): (transmembrane serine protease 6) The protein encoded by this gene is a type II transmembrane serine proteinase that is found attached to the cell surface. The encoded protein may be involved in matrix remodeling processes in the liver. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMPRSS6	NM_001374504.1	c.1442-356G>T		intron_variant		ENST00000676104.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMPRSS6	ENST00000676104.1	c.1442-356G>T		intron_variant			NM_001374504.1	P1

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88387 AN: 151806 Hom.: 26552 Cov.: 31

Gnomad AFR AF: 0.731

Gnomad AMI AF: 0.605

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.553

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.563

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.555

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

GnomAD4 genome AF: 0.582 AC: 88462 AN: 151924 Hom.: 26585 Cov.: 31 AF XY: 0.575 AC XY: 42703 AN XY: 74240

Gnomad4 AFR AF: 0.731

Gnomad4 AMR AF: 0.485

Gnomad4 ASJ AF: 0.553

Gnomad4 EAS AF: 0.461

Gnomad4 SAS AF: 0.433

Gnomad4 FIN AF: 0.563

Gnomad4 NFE AF: 0.539

Gnomad4 OTH AF: 0.549

Alfa AF: 0.409 Hom.: 3046

Bravo AF: 0.588

Asia WGS AF: 0.413 AC: 1433 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.017
Dann	Benign	0.48

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: rs2076085; hg19: chr22-37470041;