3-112047965-C-T

Variant names:

• chr3-112047965-C-T
• NM_001395507.1:c.957C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001395507.1(TMPRSS7):​c.957C>T​(p.Tyr319Tyr) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TMPRSS7 NM_001395507.1 splice_region, synonymous
• Scores: Splicing: ADA: 0.05944
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.340
• Publications: 0 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 3-112047965-C-T is Benign according to our data. Variant chr3-112047965-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2654028.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.34 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMPRSS7	NM_001395507.1	MANE Select	c.957C>T	p.Tyr319Tyr	splice_region synonymous	Exon 7 of 18	NP_001382436.1	Q7RTY8-1
	TMPRSS7	NM_001042575.2		c.579C>T	p.Tyr193Tyr	splice_region synonymous	Exon 5 of 16	NP_001036040.2	Q7RTY8-2
	TMPRSS7	NM_001366279.2		c.546C>T	p.Tyr182Tyr	splice_region synonymous	Exon 5 of 16	NP_001353208.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMPRSS7	ENST00000452346.7	TSL:5 MANE Select	c.957C>T	p.Tyr319Tyr	splice_region synonymous	Exon 7 of 18	ENSP00000398236.2	Q7RTY8-1
	TMPRSS7	ENST00000419127.5	TSL:1	c.579C>T	p.Tyr193Tyr	splice_region synonymous	Exon 5 of 16	ENSP00000411645.1	Q7RTY8-2
	TMPRSS7	ENST00000617607.4	TSL:5	c.579C>T	p.Tyr193Tyr	splice_region synonymous	Exon 4 of 15	ENSP00000478830.1	Q7RTY8-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459620 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726350

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33428

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86192

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109972

Other (OTH) AF: 0.00 AC: 0 AN: 60316

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	8.0
DANN	Benign	0.56
PhyloP100		0.34

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.059
dbscSNV1_RF	Benign	0.38
SpliceAI score (max)		0.14		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

hg19: chr3-111766812;