rs2160906

chr22-37097138-G-Achr22-37097138-G-C

Variant summary

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

The NM_001374504.1(TMPRSS6):c.337-423C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 152,170 control chromosomes in the GnomAD database, including 2,554 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 0.17 (2554 hom., cov: 33)
• Consequence: TMPRSS6 NM_001374504.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93

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 (NFE) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMPRSS6	NM_001374504.1	c.337-423C>T		intron_variant		ENST00000676104.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMPRSS6	ENST00000676104.1	c.337-423C>T		intron_variant			NM_001374504.1	P1

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26271 AN: 152050 Hom.: 2556 Cov.: 33

Gnomad AFR AF: 0.0949

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.195

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

GnomAD4 genome AF: 0.173 AC: 26279 AN: 152170 Hom.: 2554 Cov.: 33 AF XY: 0.172 AC XY: 12829 AN XY: 74396

Gnomad4 AFR AF: 0.0949

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.224

Gnomad4 EAS AF: 0.192

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.192

Alfa AF: 0.202 Hom.: 4573

Bravo AF: 0.165

Asia WGS AF: 0.148 AC: 514 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	0.031
Dann	Benign	0.68

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: rs2160906; hg19: chr22-37493178; COSMIC: COSV60983337;