22-37071314-G-C

Position:

• chr22-37071314-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.1556-282C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 151,712 control chromosomes in the GnomAD database, including 19,937 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 0.48 (19937 hom., cov: 30)
• Consequence: TMPRSS6 NM_001374504.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.735

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMPRSS6	NM_001374504.1	c.1556-282C>G		intron_variant		ENST00000676104.1	NP_001361433.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMPRSS6	ENST00000676104.1	c.1556-282C>G		intron_variant			NM_001374504.1	ENSP00000501573.1

Frequencies

GnomAD3 genomes AF: 0.483 AC: 73282 AN: 151594 Hom.: 19902 Cov.: 30

Gnomad AFR AF: 0.745

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.455

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.448

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

GnomAD4 genome AF: 0.484 AC: 73361 AN: 151712 Hom.: 19937 Cov.: 30 AF XY: 0.478 AC XY: 35410 AN XY: 74132

Gnomad4 AFR AF: 0.745

Gnomad4 AMR AF: 0.322

Gnomad4 ASJ AF: 0.413

Gnomad4 EAS AF: 0.455

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.450

Gnomad4 NFE AF: 0.390

Gnomad4 OTH AF: 0.444

Alfa AF: 0.424 Hom.: 1795

Bravo AF: 0.490

Asia WGS AF: 0.328 AC: 1138 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.77
DANN	Benign	0.40

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: rs5756505; hg19: chr22-37467354;