chr3-112045884-G-C

Variant names:

• chr3-112045884-G-C
• NM_001395507.1:c.632G>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001395507.1(TMPRSS7):​c.632G>C​(p.Arg211Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000714 in 1,399,616 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: TMPRSS7 NM_001395507.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.09

Genes affected

TMPRSS7 (HGNC:30846): (transmembrane serine protease 7) Predicted to enable serine-type peptidase activity. Predicted to be involved in proteolysis. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.79

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMPRSS7	NM_001395507.1	c.632G>C	p.Arg211Pro	missense_variant	Exon 5 of 18	ENST00000452346.7	NP_001382436.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMPRSS7	ENST00000452346.7	c.632G>C	p.Arg211Pro	missense_variant	Exon 5 of 18	5	NM_001395507.1	ENSP00000398236.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.14e-7 AC: 1 AN: 1399616 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 690292

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000126

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.019	T;.;.;.
Eigen	Uncertain	0.66
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D;.;D;D
M_CAP	Benign	0.011	T
MetaRNN	Pathogenic	0.79	D;D;D;D
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.0	M;.;.;.
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.4	N;N;.;D
REVEL	Benign	0.27
Sift	Benign	0.071	T;T;.;D
Sift4G	Benign	0.13	T;T;T;D
Polyphen		1.0	.;D;D;.
Vest4		0.70
MutPred		0.65		.;Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);.;
MVP		0.68
MPC		0.50
ClinPred		0.99	D
GERP RS		5.1
Varity_R		0.28
gMVP		0.83

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: chr3-111764731;