3-112073747-T-C

Variant names:

• chr3-112073747-T-C
• rs16859140
• NM_001395507.1:c.1667-549T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMPRSS7	NM_001395507.1	MANE Select	c.1667-549T>C		intron	N/A	NP_001382436.1
	TMPRSS7	NM_001042575.2		c.1289-549T>C		intron	N/A	NP_001036040.2
	TMPRSS7	NM_001366279.2		c.1256-549T>C		intron	N/A	NP_001353208.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMPRSS7	ENST00000452346.7	TSL:5 MANE Select	c.1667-549T>C		intron	N/A	ENSP00000398236.2
	TMPRSS7	ENST00000419127.5	TSL:1	c.1289-549T>C		intron	N/A	ENSP00000411645.1
	TMPRSS7	ENST00000617607.4	TSL:5	c.1289-549T>C		intron	N/A	ENSP00000478830.1

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

African (AFR) AF: 0.100 AC: 4170 AN: 41522

American (AMR) AF: 0.331 AC: 5053 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1016 AN: 3470

East Asian (EAS) AF: 0.434 AC: 2235 AN: 5148

South Asian (SAS) AF: 0.294 AC: 1415 AN: 4810

European-Finnish (FIN) AF: 0.304 AC: 3213 AN: 10562

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.270 AC: 18341 AN: 67976

Other (OTH) AF: 0.227 AC: 480 AN: 2110

Alfa AF: 0.266 Hom.: 2284

Bravo AF: 0.231

Asia WGS AF: 0.330 AC: 1149 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.9
DANN	Benign	0.85
PhyloP100		0.26
Mutation Taster		=100/0	polymorphism (auto)

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: rs16859140; hg19: chr3-111792594;