Variant 2-227363778-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_024795.4(TM4SF20):c.636C>T(p.Ile212Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0019 in 1,614,082 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0030 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 40 hom. )

Consequence

TM4SF20
NM_024795.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.320

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 2-227363778-G-A is Benign according to our data. Variant chr2-227363778-G-A is described in ClinVar as [Benign]. Clinvar id is 1600994.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.32 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.00178 (2609/1461872) while in subpopulation EAS AF= 0.0164 (651/39698). AF 95% confidence interval is 0.0154. There are 40 homozygotes in gnomad4_exome. There are 1288 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 460 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TM4SF20	NM_024795.4 link	c.636C>T	p.Ile212Ile	synonymous_variant	4/4	ENST00000304568.4	NP_079071.2	Q53R12
TM4SF20	XM_011511876.3 link	c.435C>T	p.Ile145Ile	synonymous_variant	5/5		XP_011510178.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TM4SF20	ENST00000304568.4 link	c.636C>T	p.Ile212Ile	synonymous_variant	4/4	1	NM_024795.4	ENSP00000303028.3		Q53R12

Frequencies

GnomAD3 genomes

AF:

0.00303

AC:

461

AN:

152092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00848

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.0343

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000691

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00380

AC:

955

AN:

251410

Hom.:

AF XY:

0.00379

AC XY:

515

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.000198

Gnomad EAS exome

AF:

0.00614

Gnomad SAS exome

AF:

0.000621

Gnomad FIN exome

AF:

0.0328

Gnomad NFE exome

AF:

0.000871

Gnomad OTH exome

AF:

0.00179

GnomAD4 exome

AF:

0.00178

AC:

2609

AN:

1461872

Hom.:

Cov.:

AF XY:

0.00177

AC XY:

1288

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.0164

Gnomad4 SAS exome

AF:

0.000417

Gnomad4 FIN exome

AF:

0.0289

Gnomad4 NFE exome

AF:

0.000268

Gnomad4 OTH exome

AF:

0.00126

GnomAD4 genome

AF:

0.00302

AC:

460

AN:

152210

Hom.:

Cov.:

AF XY:

0.00460

AC XY:

342

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00850

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.0343

Gnomad4 NFE

AF:

0.000691

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000899

Hom.:

Bravo

AF:

0.000389

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 07, 2023

- -

TM4SF20-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 17, 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

BayesDel_noAF

Benign

-0.55

CADD

Benign

3.1

DANN

Benign

0.83

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