3-112047901-A-T

Variant names:

• chr3-112047901-A-T
• rs759734398
• NM_001395507.1:c.893A>T

Variant summary

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

The NM_001395507.1(TMPRSS7):​c.893A>T​(p.Asn298Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: TMPRSS7 NM_001395507.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.51

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMPRSS7	NM_001395507.1	c.893A>T	p.Asn298Ile	missense_variant	Exon 7 of 18	ENST00000452346.7	NP_001382436.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMPRSS7	ENST00000452346.7	c.893A>T	p.Asn298Ile	missense_variant	Exon 7 of 18	5	NM_001395507.1	ENSP00000398236.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000401 AC: 1 AN: 249516 Hom.: 0 AF XY: 0.00000739 AC XY: 1 AN XY: 135354

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461868 Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6 AN XY: 727236

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: 0.0000696

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000826 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.070	T;.;.;.
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.87	D;.;D;D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.50	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M;.;.;.
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-3.2	D;D;.;D
REVEL	Benign	0.19
Sift	Benign	0.036	D;D;.;D
Sift4G	Uncertain	0.016	D;D;D;D
Polyphen		1.0	D;D;D;.
Vest4		0.74
MutPred		0.58		Gain of catalytic residue at E295 (P = 0.3506);.;.;.;
MVP		0.63
MPC		0.29
ClinPred		0.96	D
GERP RS		4.2
Varity_R		0.35
gMVP		0.45

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: rs759734398; hg19: chr3-111766748;