22-37082214-A-G

Position:

• chr22-37082214-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.1196+2081T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 152,094 control chromosomes in the GnomAD database, including 33,315 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 0.64 (33315 hom., cov: 32)
• Consequence: TMPRSS6 NM_001374504.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.669

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.863 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMPRSS6	NM_001374504.1	c.1196+2081T>C		intron_variant		ENST00000676104.1	NP_001361433.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMPRSS6	ENST00000676104.1	c.1196+2081T>C		intron_variant			NM_001374504.1	ENSP00000501573	P1
	ENST00000414203.2	n.194-265A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.644 AC: 97811 AN: 151976 Hom.: 33262 Cov.: 32

Gnomad AFR AF: 0.871

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.492

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.677

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.580

Gnomad OTH AF: 0.602

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

GnomAD4 genome AF: 0.644 AC: 97911 AN: 152094 Hom.: 33315 Cov.: 32 AF XY: 0.641 AC XY: 47677 AN XY: 74336

Gnomad4 AFR AF: 0.871

Gnomad4 AMR AF: 0.442

Gnomad4 ASJ AF: 0.529

Gnomad4 EAS AF: 0.493

Gnomad4 SAS AF: 0.468

Gnomad4 FIN AF: 0.677

Gnomad4 NFE AF: 0.580

Gnomad4 OTH AF: 0.594

Alfa AF: 0.562 Hom.: 18252

Bravo AF: 0.639

Asia WGS AF: 0.459 AC: 1597 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	0.33
DANN	Benign	0.37

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: rs1005478; hg19: chr22-37478254; COSMIC: COSV60974848; COSMIC: COSV60974848;