rs855791

Positions:

• chr22-37066896-A-C
• chr22-37066896-A-G
• chr22-37066896-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001374504.1(TMPRSS6):​c.2180T>G​(p.Val727Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V727A) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TMPRSS6 NM_001374504.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.84

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMPRSS6	NM_001374504.1	c.2180T>G	p.Val727Gly	missense_variant	17/18	ENST00000676104.1	NP_001361433.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMPRSS6	ENST00000676104.1	c.2180T>G	p.Val727Gly	missense_variant	17/18		NM_001374504.1	ENSP00000501573	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 62

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.041	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.53	D;.;.;.
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.14	T;T;T;.
M_CAP	Uncertain	0.092	D
MetaRNN	Uncertain	0.50	D;D;D;D
MetaSVM	Uncertain	-0.10	T
MutationAssessor	Benign	0.055	N;.;.;.
MutationTaster	Benign	0.015	P;P;P;P
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-2.5	N;D;N;D
REVEL	Uncertain	0.37
Sift	Benign	0.16	T;T;T;T
Sift4G	Uncertain	0.027	D;D;D;D
Polyphen		0.0	B;B;.;B
Vest4		0.16
MutPred		0.53		Loss of stability (P = 0.0032);.;.;.;
MVP		0.76
MPC		0.21
ClinPred		0.92	D
GERP RS		4.7
Varity_R		0.27
gMVP		0.39

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-37462936;