3-112073747-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001395507.1(TMPRSS7):c.1667-549T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 152,076 control chromosomes in the GnomAD database, including 4,949 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 0.24 (4949 hom., cov: 32)
• Consequence: TMPRSS7 NM_001395507.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.261

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMPRSS7	NM_001395507.1	c.1667-549T>C		intron_variant		ENST00000452346.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMPRSS7	ENST00000452346.7	c.1667-549T>C		intron_variant		5	NM_001395507.1
TMPRSS7	ENST00000419127.5	c.1289-549T>C		intron_variant		1		P1
TMPRSS7	ENST00000617607.4	c.1289-549T>C		intron_variant		5		P1
TMPRSS7	ENST00000435737.5	c.*1012-549T>C		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36212 AN: 151958 Hom.: 4942 Cov.: 32

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.227

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

GnomAD4 genome AF: 0.238 AC: 36236 AN: 152076 Hom.: 4949 Cov.: 32 AF XY: 0.244 AC XY: 18120 AN XY: 74340

Gnomad4 AFR AF: 0.100

Gnomad4 AMR AF: 0.331

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.434

Gnomad4 SAS AF: 0.294

Gnomad4 FIN AF: 0.304

Gnomad4 NFE AF: 0.270

Gnomad4 OTH AF: 0.227

Alfa AF: 0.259 Hom.: 1265

Bravo AF: 0.231

Asia WGS AF: 0.330 AC: 1149 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	7.9
Dann	Benign	0.85

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: rs16859140; hg19: chr3-111792594;