rs4806846

Variant names:

• chr19-2410486-G-A
• rs4806846
• NM_001395513.1:c.1254+92G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-2410486-G-A
• chr19-2410486-G-C

Variant summary

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

The NM_001395513.1(TMPRSS9):​c.1254+92G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,501,352 control chromosomes in the GnomAD database, including 19,735 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 0.13 (2006 hom., cov: 31)
  • Exomes 𝑓: 0.15 (17729 hom.)
• Consequence: TMPRSS9 NM_001395513.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.918
• Publications: 7 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]

TMPRSS9 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
• neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

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.1254+92G>A		intron	N/A	NP_001382442.1	A0A3B3IU58
	TMPRSS9	NM_182973.3		c.1152+92G>A		intron	N/A	NP_892018.1	Q7Z410
	TMPRSS9	NM_001385642.1		c.558+92G>A		intron	N/A	NP_001372571.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMPRSS9	ENST00000696167.1	MANE Select	c.1254+92G>A		intron	N/A	ENSP00000512457.1	A0A3B3IU58
	TMPRSS9	ENST00000395264.3	TSL:1	n.1269+92G>A		intron	N/A
	TMPRSS9	ENST00000648592.1		c.1254+92G>A		intron	N/A	ENSP00000498031.1	A0A3B3IU58

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20402 AN: 151894 Hom.: 1996 Cov.: 31

Gnomad AFR AF: 0.0336

Gnomad AMI AF: 0.0978

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.137

GnomAD4 exome AF: 0.151 AC: 203302 AN: 1349340 Hom.: 17729 AF XY: 0.149 AC XY: 99275 AN XY: 664164

African (AFR) AF: 0.0242 AC: 746 AN: 30768

American (AMR) AF: 0.417 AC: 14621 AN: 35098

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 3529 AN: 23072

East Asian (EAS) AF: 0.234 AC: 8357 AN: 35790

South Asian (SAS) AF: 0.159 AC: 11977 AN: 75556

European-Finnish (FIN) AF: 0.197 AC: 7280 AN: 37036

Middle Eastern (MID) AF: 0.112 AC: 611 AN: 5472

European-Non Finnish (NFE) AF: 0.140 AC: 147536 AN: 1050154

Other (OTH) AF: 0.153 AC: 8645 AN: 56394

GnomAD4 genome AF: 0.134 AC: 20429 AN: 152012 Hom.: 2006 Cov.: 31 AF XY: 0.142 AC XY: 10520 AN XY: 74290

African (AFR) AF: 0.0335 AC: 1390 AN: 41506

American (AMR) AF: 0.296 AC: 4509 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 538 AN: 3466

East Asian (EAS) AF: 0.250 AC: 1295 AN: 5178

South Asian (SAS) AF: 0.153 AC: 736 AN: 4808

European-Finnish (FIN) AF: 0.202 AC: 2131 AN: 10566

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.139 AC: 9423 AN: 67956

Other (OTH) AF: 0.134 AC: 282 AN: 2098

Alfa AF: 0.138 Hom.: 476

Bravo AF: 0.141

Asia WGS AF: 0.200 AC: 694 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.5
DANN	Benign	0.76
PhyloP100		-0.92
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4806846;

hg19: chr19-2410484;

COSMIC: COSV60225544;