rs2076085

Variant names:

• chr22-37074001-C-A
• rs2076085
• NM_001374504.1:c.1442-356G>T

Your query was ambiguous. Multiple possible variants found:

• chr22-37074001-C-A
• chr22-37074001-C-G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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]

TMPRSS6 Gene-Disease associations (from GenCC):

• IRIDA syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TMPRSS6	NM_001374504.1	c.1442-356G>T		intron_variant	Intron 12 of 17	ENST00000676104.1	NP_001361433.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMPRSS6	ENST00000676104.1	c.1442-356G>T		intron_variant	Intron 12 of 17		NM_001374504.1	ENSP00000501573.1

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

African (AFR) AF: 0.731 AC: 30297 AN: 41454

American (AMR) AF: 0.485 AC: 7408 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.553 AC: 1916 AN: 3466

East Asian (EAS) AF: 0.461 AC: 2374 AN: 5152

South Asian (SAS) AF: 0.433 AC: 2081 AN: 4802

European-Finnish (FIN) AF: 0.563 AC: 5929 AN: 10528

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.539 AC: 36588 AN: 67932

Other (OTH) AF: 0.549 AC: 1157 AN: 2108

Alfa AF: 0.418 Hom.: 3243

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
PhyloP100		-2.7
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: rs2076085; hg19: chr22-37470041;