chr19-2425959-G-A

Variant names:

• chr19-2425959-G-A
• rs746183325
• NM_001395513.1:c.3153G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001395513.1(TMPRSS9):​c.3153G>A​(p.Glu1051Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,451,050 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TMPRSS9 NM_001395513.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.245
• Publications: 1 publications found

Genes affected

TMPRSS9 (HGNC:30079): (transmembrane serine protease 9) The protein encoded by this gene is a membrane-bound type II serine polyprotease that is cleaved to release three different proteases. Two of the proteases are active and can be inhibited by serine protease inhibitors, and one is thought to be catalytically inactive. This gene enhances the invasive capability of pancreatic cancer cells and may be involved in cancer progression. [provided by RefSeq, Jul 2016]

TIMM13 (HGNC:11816): (translocase of inner mitochondrial membrane 13) This gene encodes a member of the evolutionarily conserved TIMM (translocase of inner mitochondrial membrane) family of proteins that function as chaperones in the import of proteins from the cytoplasm into the mitochondrial inner membrane. Proteins of this family play a role in collecting substrate proteins from the translocase of the outer mitochondrial membrane (TOM) complex and delivering them to either the sorting and assembly machinery in the outer mitochondrial membrane (SAM) complex or the TIMM22 complex in the inner mitochondrial membrane. The encoded protein and the translocase of mitochondrial inner membrane 8a protein form a 70 kDa complex in the intermembrane space. [provided by RefSeq, Jul 2013]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP7: Synonymous conserved (PhyloP=0.245 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395513.1. 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
	TMPRSS9	NM_001395513.1	MANE Select	c.3153G>A	p.Glu1051Glu	synonymous	Exon 19 of 19	NP_001382442.1	A0A3B3IU58
	TIMM13	NM_012458.4	MANE Select	c.*989C>T		3_prime_UTR	Exon 3 of 3	NP_036590.1	Q9Y5L4
	TMPRSS9	NM_182973.3		c.3051G>A	p.Glu1017Glu	synonymous	Exon 18 of 18	NP_892018.1	Q7Z410

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMPRSS9	ENST00000696167.1	MANE Select	c.3153G>A	p.Glu1051Glu	synonymous	Exon 19 of 19	ENSP00000512457.1	A0A3B3IU58
	TIMM13	ENST00000215570.8	TSL:1 MANE Select	c.*989C>T		3_prime_UTR	Exon 3 of 3	ENSP00000215570.2	Q9Y5L4
	TMPRSS9	ENST00000648592.1		c.3153G>A	p.Glu1051Glu	synonymous	Exon 18 of 18	ENSP00000498031.1	A0A3B3IU58

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000419 AC: 1 AN: 238800 AF XY: 0.00000769

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000320

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1451050 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 722028

African (AFR) AF: 0.00 AC: 0 AN: 32816

American (AMR) AF: 0.0000241 AC: 1 AN: 41522

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25576

East Asian (EAS) AF: 0.00 AC: 0 AN: 39428

South Asian (SAS) AF: 0.00 AC: 0 AN: 85070

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5488

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108634

Other (OTH) AF: 0.00 AC: 0 AN: 59930

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	7.3
DANN	Benign	0.72
PhyloP100		0.24
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8

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: rs746183325; hg19: chr19-2425957;