Variant 20-32149726-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_014742.4(TM9SF4):c.1047C>T(p.Gly349Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00285 in 1,614,212 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0030 ( 12 hom. )

Consequence

TM9SF4
NM_014742.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.835

Variant links:

Genes affected

TM9SF4 (HGNC:30797): (transmembrane 9 superfamily member 4) Involved in several processes, including positive regulation of protein localization; regulation of intracellular pH; and vacuolar proton-transporting V-type ATPase complex assembly. Located in Golgi apparatus and early endosome. [provided by Alliance of Genome Resources, Apr 2022]

TM9SF4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 20-32149726-C-T is Benign according to our data. Variant chr20-32149726-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3388342.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.835 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 12 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TM9SF4	NM_014742.4 linkuse as main transcript	c.1047C>T	p.Gly349Gly	synonymous_variant	10/18	ENST00000398022.7	NP_055557.2	Q92544A0A024QYR3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TM9SF4	ENST00000398022.7 linkuse as main transcript	c.1047C>T	p.Gly349Gly	synonymous_variant	10/18	1	NM_014742.4	ENSP00000381104.2		Q92544
TM9SF4	ENST00000217315.9 linkuse as main transcript	c.996C>T	p.Gly332Gly	synonymous_variant	10/18	2		ENSP00000217315.5		A0A0C4DFM1

Frequencies

GnomAD3 genomes

AF:

0.00173

AC:

264

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00318

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00150

AC:

376

AN:

251340

Hom.:

AF XY:

0.00142

AC XY:

193

AN XY:

135856

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.00110

Gnomad ASJ exome

AF:

0.00546

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00235

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00297

AC:

4339

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00287

AC XY:

2086

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.000388

Gnomad4 AMR exome

AF:

0.00103

Gnomad4 ASJ exome

AF:

0.00528

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000936

Gnomad4 NFE exome

AF:

0.00356

Gnomad4 OTH exome

AF:

0.00293

GnomAD4 genome

AF:

0.00173

AC:

264

AN:

152336

Hom.:

Cov.:

AF XY:

0.00179

AC XY:

133

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.000577

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00318

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00255

Hom.:

Bravo

AF:

0.00168

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00311

EpiControl

AF:

0.00279

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2024

TM9SF4: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.67

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over