3-112041926-C-T

Variant names:

• chr3-112041926-C-T
• rs11929695
• NM_001395507.1:c.305C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001395507.1(TMPRSS7):​c.305C>T​(p.Thr102Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0989 in 1,539,698 control chromosomes in the GnomAD database, including 9,253 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.12 (1315 hom., cov: 32)
  • Exomes 𝑓: 0.097 (7938 hom.)
• Consequence: TMPRSS7 NM_001395507.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.47

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 (MetaRNN=0.0027706027).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMPRSS7	NM_001395507.1	c.305C>T	p.Thr102Ile	missense_variant	Exon 3 of 18	ENST00000452346.7	NP_001382436.1
TMPRSS7	XM_011512754.2	c.56C>T	p.Thr19Ile	missense_variant	Exon 2 of 17		XP_011511056.1
TMPRSS7	NM_001042575.2	c.-32C>T		5_prime_UTR_variant	Exon 2 of 16		NP_001036040.2
TMPRSS7	NR_026734.1	n.139C>T		non_coding_transcript_exon_variant	Exon 2 of 17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMPRSS7	ENST00000452346.7	c.305C>T	p.Thr102Ile	missense_variant	Exon 3 of 18	5	NM_001395507.1	ENSP00000398236.2

Frequencies

GnomAD3 genomes AF: 0.118 AC: 18005 AN: 152108 Hom.: 1310 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.0845

Gnomad ASJ AF: 0.0960

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.0600

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0815

Gnomad OTH AF: 0.0946

GnomAD2 exomes AF: 0.111 AC: 17285 AN: 156264 AF XY: 0.117

Gnomad AFR exome AF: 0.190

Gnomad AMR exome AF: 0.0743

Gnomad ASJ exome AF: 0.0987

Gnomad EAS exome AF: 0.111

Gnomad FIN exome AF: 0.0626

Gnomad NFE exome AF: 0.0824

Gnomad OTH exome AF: 0.0931

GnomAD4 exome AF: 0.0968 AC: 134241 AN: 1387472 Hom.: 7938 Cov.: 30 AF XY: 0.101 AC XY: 68912 AN XY: 685070

Gnomad4 AFR exome AF: 0.193 AC: 6047 AN: 31336

Gnomad4 AMR exome AF: 0.0750 AC: 2675 AN: 35674

Gnomad4 ASJ exome AF: 0.0953 AC: 2389 AN: 25066

Gnomad4 EAS exome AF: 0.100 AC: 3567 AN: 35676

Gnomad4 SAS exome AF: 0.242 AC: 19081 AN: 79000

Gnomad4 FIN exome AF: 0.0581 AC: 2858 AN: 49222

Gnomad4 NFE exome AF: 0.0850 AC: 90804 AN: 1068224

Gnomad4 Remaining exome AF: 0.110 AC: 6337 AN: 57598

GnomAD4 genome AF: 0.118 AC: 18034 AN: 152226 Hom.: 1315 Cov.: 32 AF XY: 0.120 AC XY: 8930 AN XY: 74428

Gnomad4 AFR AF: 0.193 AC: 0.192876 AN: 0.192876

Gnomad4 AMR AF: 0.0842 AC: 0.0841623 AN: 0.0841623

Gnomad4 ASJ AF: 0.0960 AC: 0.0959654 AN: 0.0959654

Gnomad4 EAS AF: 0.117 AC: 0.117194 AN: 0.117194

Gnomad4 SAS AF: 0.267 AC: 0.266722 AN: 0.266722

Gnomad4 FIN AF: 0.0600 AC: 0.0599661 AN: 0.0599661

Gnomad4 NFE AF: 0.0815 AC: 0.0814565 AN: 0.0814565

Gnomad4 OTH AF: 0.101 AC: 0.10123 AN: 0.10123

Alfa AF: 0.0951 Hom.: 1417

Bravo AF: 0.117

TwinsUK AF: 0.0785 AC: 291

ALSPAC AF: 0.0882 AC: 340

ESP6500AA AF: 0.192 AC: 266

ESP6500EA AF: 0.0801 AC: 255

ExAC AF: 0.137 AC: 3261

Asia WGS AF: 0.208 AC: 724 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.027	T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.75	T
MetaRNN	Benign	0.0028	T
MetaSVM	Benign	-1.2	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.040
Sift	Benign	0.076	T
Sift4G	Benign	0.18	T
Vest4		0.11
ClinPred		0.016	T
GERP RS		5.5
Varity_R		0.14
Mutation Taster		=268/32	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs11929695; hg19: chr3-111760773; COSMIC: COSV107517881; COSMIC: COSV107517881;