3-112049902-G-A

Variant names:

• chr3-112049902-G-A
• rs774765903
• NM_001395507.1:c.1018G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001395507.1(TMPRSS7):​c.1018G>A​(p.Val340Met) variant causes a missense change. The variant allele was found at a frequency of 0.000000711 in 1,406,808 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V340L) has been classified as Uncertain significance.

• 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: 3.94
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.794

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395507.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMPRSS7	NM_001395507.1	MANE Select	c.1018G>A	p.Val340Met	missense	Exon 8 of 18	NP_001382436.1	Q7RTY8-1
	TMPRSS7	NM_001042575.2		c.640G>A	p.Val214Met	missense	Exon 6 of 16	NP_001036040.2	Q7RTY8-2
	TMPRSS7	NM_001366279.2		c.607G>A	p.Val203Met	missense	Exon 6 of 16	NP_001353208.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMPRSS7	ENST00000452346.7	TSL:5 MANE Select	c.1018G>A	p.Val340Met	missense	Exon 8 of 18	ENSP00000398236.2	Q7RTY8-1
	TMPRSS7	ENST00000419127.5	TSL:1	c.640G>A	p.Val214Met	missense	Exon 6 of 16	ENSP00000411645.1	Q7RTY8-2
	TMPRSS7	ENST00000617607.4	TSL:5	c.640G>A	p.Val214Met	missense	Exon 5 of 15	ENSP00000478830.1	Q7RTY8-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000409 AC: 1 AN: 244378 AF XY: 0.00000754

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.11e-7 AC: 1 AN: 1406808 Hom.: 0 Cov.: 30 AF XY: 0.00000144 AC XY: 1 AN XY: 694636

African (AFR) AF: 0.00 AC: 0 AN: 32714

American (AMR) AF: 0.00 AC: 0 AN: 43544

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24880

East Asian (EAS) AF: 0.00 AC: 0 AN: 38680

South Asian (SAS) AF: 0.0000127 AC: 1 AN: 78722

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51814

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5554

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1073358

Other (OTH) AF: 0.00 AC: 0 AN: 57542

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000828 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.37
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.026	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.023	T
MetaRNN	Pathogenic	0.79	D
MetaSVM	Benign	-0.84	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		3.9
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.28
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.014	D
Polyphen		1.0	D
Vest4		0.68
MutPred		0.65		Gain of methylation at K343 (P = 0.1385)
MVP		0.55
MPC		0.40
ClinPred		0.91	D
GERP RS		4.3
Varity_R		0.15
gMVP		0.54
Mutation Taster		=75/25	polymorphism

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

Other links and lift over

dbSNP: rs774765903; hg19: chr3-111768749;