22-37071352-G-C

Position:

• chr22-37071352-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.1556-320C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 151,998 control chromosomes in the GnomAD database, including 18,834 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 0.47 (18834 hom., cov: 32)
• Consequence: TMPRSS6 NM_001374504.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.218

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMPRSS6	NM_001374504.1	c.1556-320C>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.1556-320C>G		intron_variant			NM_001374504.1	ENSP00000501573.1

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70612 AN: 151880 Hom.: 18800 Cov.: 32

Gnomad AFR AF: 0.740

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.455

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.426

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

GnomAD4 genome AF: 0.465 AC: 70690 AN: 151998 Hom.: 18834 Cov.: 32 AF XY: 0.459 AC XY: 34088 AN XY: 74292

Gnomad4 AFR AF: 0.740

Gnomad4 AMR AF: 0.302

Gnomad4 ASJ AF: 0.390

Gnomad4 EAS AF: 0.456

Gnomad4 SAS AF: 0.263

Gnomad4 FIN AF: 0.415

Gnomad4 NFE AF: 0.363

Gnomad4 OTH AF: 0.422

Alfa AF: 0.229 Hom.: 453

Bravo AF: 0.474

Asia WGS AF: 0.324 AC: 1125 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.5
DANN	Benign	0.65

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: rs5756506; hg19: chr22-37467392;