3-112050311-T-C

Variant names:

• chr3-112050311-T-C
• rs2399403
• NM_001395507.1:c.1090+337T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001395507.1(TMPRSS7):​c.1090+337T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0354 in 152,014 control chromosomes in the GnomAD database, including 141 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.035 (141 hom., cov: 31)
• Consequence: TMPRSS7 NM_001395507.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.155
• Publications: 3 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0354 (5376/152014) while in subpopulation NFE AF = 0.0485 (3294/67942). AF 95% confidence interval is 0.0471. There are 141 homozygotes in GnomAd4. There are 2653 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 141 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMPRSS7	NM_001395507.1	c.1090+337T>C		intron_variant	Intron 8 of 17	ENST00000452346.7	NP_001382436.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMPRSS7	ENST00000452346.7	c.1090+337T>C		intron_variant	Intron 8 of 17	5	NM_001395507.1	ENSP00000398236.2
TMPRSS7	ENST00000419127.5	c.712+337T>C		intron_variant	Intron 6 of 15	1		ENSP00000411645.1
TMPRSS7	ENST00000617607.4	c.712+337T>C		intron_variant	Intron 5 of 14	5		ENSP00000478830.1
TMPRSS7	ENST00000435737.5	n.*435+337T>C		intron_variant	Intron 7 of 16	2		ENSP00000415472.1

Frequencies

GnomAD3 genomes AF: 0.0354 AC: 5379 AN: 151896 Hom.: 141 Cov.: 31

Gnomad AFR AF: 0.00810

Gnomad AMI AF: 0.0771

Gnomad AMR AF: 0.0298

Gnomad ASJ AF: 0.0493

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0284

Gnomad FIN AF: 0.0787

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0485

Gnomad OTH AF: 0.0384

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0354 AC: 5376 AN: 152014 Hom.: 141 Cov.: 31 AF XY: 0.0357 AC XY: 2653 AN XY: 74298

African (AFR) AF: 0.00807 AC: 335 AN: 41498

American (AMR) AF: 0.0297 AC: 454 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0493 AC: 171 AN: 3468

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5164

South Asian (SAS) AF: 0.0284 AC: 137 AN: 4816

European-Finnish (FIN) AF: 0.0787 AC: 830 AN: 10550

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0485 AC: 3294 AN: 67942

Other (OTH) AF: 0.0380 AC: 80 AN: 2104

Alfa AF: 0.0439 Hom.: 136

Bravo AF: 0.0315

Asia WGS AF: 0.0120 AC: 42 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.8
DANN	Benign	0.53
PhyloP100		-0.15
Mutation Taster		=100/0	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: rs2399403; hg19: chr3-111769158;