3-112045919-G-C

Variant names:

• chr3-112045919-G-C
• NM_001395507.1:c.667G>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001395507.1(TMPRSS7):​c.667G>C​(p.Asp223His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: TMPRSS7 NM_001395507.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.935

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMPRSS7	NM_001395507.1	c.667G>C	p.Asp223His	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.667G>C	p.Asp223His	missense_variant	Exon 5 of 18	5	NM_001395507.1	ENSP00000398236.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 12, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.328G>C (p.D110H) alteration is located in exon 4 (coding exon 3) of the TMPRSS7 gene. This alteration results from a G to C substitution at nucleotide position 328, causing the aspartic acid (D) at amino acid position 110 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T;.;.;.
Eigen	Uncertain	0.62
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D;.;D;D
M_CAP	Benign	0.013	T
MetaRNN	Pathogenic	0.93	D;D;D;D
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.0	M;.;.;.
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-2.7	D;N;.;D
REVEL	Uncertain	0.50
Sift	Uncertain	0.016	D;D;.;D
Sift4G	Uncertain	0.018	D;D;D;D
Polyphen		1.0	.;D;D;.
Vest4		0.74
MutPred		0.84		.;Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);.;
MVP		0.73
MPC		0.45
ClinPred		0.99	D
GERP RS		5.1
Varity_R		0.27
gMVP		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr3-111764766;