2-227379189-G-A

Position:

chr2-227379189-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_024795.4(TM4SF20):c.80C>T(p.Ala27Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 1,613,730 control chromosomes in the GnomAD database, including 13,573 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.11 ( 1045 hom., cov: 33)

Exomes 𝑓: 0.13 ( 12528 hom. )

Consequence

TM4SF20
NM_024795.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.102

Variant links:

Genes affected

TM4SF20 (HGNC:26230): (transmembrane 4 L six family member 20) The protein encoded by this gene is a member of the four-transmembrane L6 superfamily. Members of this family function in various cellular processes including cell proliferation, motility, and adhesion via their interactions with integrins. In human brain tissue, this gene is expressed at high levels in the parietal lobe, occipital lobe, hippocampus, pons, white matter, corpus callosum, and cerebellum. Knockout of the homologous gene in mouse results in a neurobehavioral phenotype with suggested enhanced motor coordination. A deletion mutation in the human gene is associated with specific language impairment-5. [provided by RefSeq, Jul 2016]

TM4SF20 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022626221).

BP6

Variant 2-227379189-G-A is Benign according to our data. Variant chr2-227379189-G-A is described in ClinVar as [Benign]. Clinvar id is 1166272.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TM4SF20	NM_024795.4 linkuse as main transcript	c.80C>T	p.Ala27Val	missense_variant	1/4	ENST00000304568.4	NP_079071.2	Q53R12
TM4SF20	XM_011511876.3 linkuse as main transcript	c.-205+2400C>T		intron_variant			XP_011510178.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TM4SF20	ENST00000304568.4 linkuse as main transcript	c.80C>T	p.Ala27Val	missense_variant	1/4	1	NM_024795.4	ENSP00000303028.3		Q53R12
TM4SF20	ENST00000449706.1 linkuse as main transcript	c.*37C>T		downstream_gene_variant		4		ENSP00000416565.1		C9JES4

Frequencies

GnomAD3 genomes

AF:

0.107

AC:

16249

AN:

152000

Hom.:

1046

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0238

Gnomad AMI

AF:

0.285

Gnomad AMR

AF:

0.0964

Gnomad ASJ

AF:

0.159

Gnomad EAS

AF:

0.190

Gnomad SAS

AF:

0.100

Gnomad FIN

AF:

0.156

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.141

Gnomad OTH

AF:

0.128

GnomAD3 exomes

AF:

0.122

AC:

30744

AN:

251312

Hom.:

2094

AF XY:

0.125

AC XY:

16922

AN XY:

135822

show subpopulations

Gnomad AFR exome

AF:

0.0230

Gnomad AMR exome

AF:

0.0729

Gnomad ASJ exome

AF:

0.150

Gnomad EAS exome

AF:

0.186

Gnomad SAS exome

AF:

0.0924

Gnomad FIN exome

AF:

0.158

Gnomad NFE exome

AF:

0.139

Gnomad OTH exome

AF:

0.136

GnomAD4 exome

AF:

0.130

AC:

189304

AN:

1461612

Hom.:

12528

Cov.:

AF XY:

0.130

AC XY:

94218

AN XY:

727098

show subpopulations

Gnomad4 AFR exome

AF:

0.0209

Gnomad4 AMR exome

AF:

0.0737

Gnomad4 ASJ exome

AF:

0.144

Gnomad4 EAS exome

AF:

0.179

Gnomad4 SAS exome

AF:

0.0911

Gnomad4 FIN exome

AF:

0.157

Gnomad4 NFE exome

AF:

0.135

Gnomad4 OTH exome

AF:

0.128

GnomAD4 genome

AF:

0.107

AC:

16251

AN:

152118

Hom.:

1045

Cov.:

AF XY:

0.107

AC XY:

7989

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.0237

Gnomad4 AMR

AF:

0.0965

Gnomad4 ASJ

AF:

0.159

Gnomad4 EAS

AF:

0.191

Gnomad4 SAS

AF:

0.100

Gnomad4 FIN

AF:

0.156

Gnomad4 NFE

AF:

0.141

Gnomad4 OTH

AF:

0.128

Alfa

AF:

0.134

Hom.:

2898

Bravo

AF:

0.0998

TwinsUK

AF:

0.133

AC:

492

ALSPAC

AF:

0.124

AC:

479

ESP6500AA

AF:

0.0261

AC:

115

ESP6500EA

AF:

0.141

AC:

1209

ExAC

AF:

0.122

AC:

14819

Asia WGS

AF:

0.142

AC:

491

AN:

3478

EpiCase

AF:

0.150

EpiControl

AF:

0.146

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -

TM4SF20-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 22, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.68

CADD

Benign

2.4

DANN

Benign

0.073

DEOGEN2

Benign

0.0028

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.041

LIST_S2

Benign

0.59

MetaRNN

Benign

0.0023

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PrimateAI

Benign

0.30

PROVEAN

Benign

1.5

REVEL

Benign

0.076

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.96

Vest4

0.030

MPC

0.011

ClinPred

0.016

GERP RS

1.8

Varity_R

0.022

gMVP

0.25

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