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GeneBe

rs855791

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

Scores

9
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.84
Variant links:
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]

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ACMG classification

Classification made for transcript

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 UniProt
TMPRSS6NM_001374504.1 linkuse as main transcriptc.2180T>G p.Val727Gly missense_variant 17/18 ENST00000676104.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TMPRSS6ENST00000676104.1 linkuse as main transcriptc.2180T>G p.Val727Gly missense_variant 17/18 NM_001374504.1 P1Q8IU80-1

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; API