3-112047867-C-T

Variant names:

• chr3-112047867-C-T
• NM_001395507.1:c.859C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001395507.1(TMPRSS7):​c.859C>T​(p.Leu287Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,866 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TMPRSS7 NM_001395507.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.08
• 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 2 ACMG points.

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

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.859C>T	p.Leu287Phe	missense	Exon 7 of 18	NP_001382436.1	Q7RTY8-1
	TMPRSS7	NM_001042575.2		c.481C>T	p.Leu161Phe	missense	Exon 5 of 16	NP_001036040.2	Q7RTY8-2
	TMPRSS7	NM_001366279.2		c.448C>T	p.Leu150Phe	missense	Exon 5 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.859C>T	p.Leu287Phe	missense	Exon 7 of 18	ENSP00000398236.2	Q7RTY8-1
	TMPRSS7	ENST00000419127.5	TSL:1	c.481C>T	p.Leu161Phe	missense	Exon 5 of 16	ENSP00000411645.1	Q7RTY8-2
	TMPRSS7	ENST00000617607.4	TSL:5	c.481C>T	p.Leu161Phe	missense	Exon 4 of 15	ENSP00000478830.1	Q7RTY8-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461866 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727236

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111994

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.055	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.090	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.084
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.71	D
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		4.1
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.21
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.012	D
Polyphen		0.035	B
Vest4		0.44
MutPred		0.79		Loss of catalytic residue at L287 (P = 0.0319)
MVP		0.48
MPC		0.11
ClinPred		0.96	D
GERP RS		3.5
Varity_R		0.22
gMVP		0.52
Mutation Taster		=68/32	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

hg19: chr3-111766714;