22-37091770-A-G

Position:

• chr22-37091770-A-G

Variant summary

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

The NM_001374504.1(TMPRSS6):​c.632-1988T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 152,080 control chromosomes in the GnomAD database, including 16,093 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 0.45 (16093 hom., cov: 32)
• Consequence: TMPRSS6 NM_001374504.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0870

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMPRSS6	NM_001374504.1	c.632-1988T>C		intron_variant		ENST00000676104.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMPRSS6	ENST00000676104.1	c.632-1988T>C		intron_variant			NM_001374504.1	P1

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68328 AN: 151962 Hom.: 16077 Cov.: 32

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.418

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

GnomAD4 genome AF: 0.450 AC: 68387 AN: 152080 Hom.: 16093 Cov.: 32 AF XY: 0.452 AC XY: 33627 AN XY: 74330

Gnomad4 AFR AF: 0.593

Gnomad4 AMR AF: 0.382

Gnomad4 ASJ AF: 0.337

Gnomad4 EAS AF: 0.416

Gnomad4 SAS AF: 0.470

Gnomad4 FIN AF: 0.431

Gnomad4 NFE AF: 0.389

Gnomad4 OTH AF: 0.412

Alfa AF: 0.395 Hom.: 15989

Bravo AF: 0.450

Asia WGS AF: 0.416 AC: 1443 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.9
DANN	Benign	0.58

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: rs1421312; hg19: chr22-37487810;