chr3-112041926-C-T

Position:

• chr3-112041926-C-T

Variant summary

Our verdict is Benign. Variant got -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. 10/15 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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
TMPRSS7	NM_001395507.1	c.305C>T	p.Thr102Ile	missense_variant	3/18	ENST00000452346.7
TMPRSS7	XM_011512754.2	c.56C>T	p.Thr19Ile	missense_variant	2/17
TMPRSS7	NM_001042575.2	c.-32C>T		5_prime_UTR_variant	2/16
TMPRSS7	NR_026734.1	n.139C>T		non_coding_transcript_exon_variant	2/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMPRSS7	ENST00000452346.7	c.305C>T	p.Thr102Ile	missense_variant	3/18	5	NM_001395507.1
TMPRSS7	ENST00000419127.5	c.-32C>T		5_prime_UTR_variant	2/16	1		P1
TMPRSS7	ENST00000617607.4	c.-32C>T		5_prime_UTR_variant	1/15	5		P1
TMPRSS7	ENST00000435737.5	c.-32C>T		5_prime_UTR_variant, NMD_transcript_variant	2/17	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

GnomAD3 exomes AF: 0.111 AC: 17285 AN: 156264 Hom.: 1304 AF XY: 0.117 AC XY: 9715 AN XY: 82818

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 SAS exome AF: 0.241

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

Gnomad4 AMR exome AF: 0.0750

Gnomad4 ASJ exome AF: 0.0953

Gnomad4 EAS exome AF: 0.100

Gnomad4 SAS exome AF: 0.242

Gnomad4 FIN exome AF: 0.0581

Gnomad4 NFE exome AF: 0.0850

Gnomad4 OTH exome AF: 0.110

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

Gnomad4 AMR AF: 0.0842

Gnomad4 ASJ AF: 0.0960

Gnomad4 EAS AF: 0.117

Gnomad4 SAS AF: 0.267

Gnomad4 FIN AF: 0.0600

Gnomad4 NFE AF: 0.0815

Gnomad4 OTH AF: 0.101

Alfa AF: 0.0948 Hom.: 339

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
MutationTaster	Benign	0.91	P;P
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

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;