Variant 6-31874821-T-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000229729.11(SLC44A4):c.368A>T(p.Asp123Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 1,612,436 control chromosomes in the GnomAD database, including 16,109 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 ( 1324 hom., cov: 31)

Exomes 𝑓: 0.14 ( 14785 hom. )

Consequence

SLC44A4
ENST00000229729.11 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.87

Variant links:

Genes affected

SLC44A4 (HGNC:13941): (solute carrier family 44 member 4) The protein encoded by this gene may be a sodium-dependent transmembrane transport protein involved in the uptake of choline by cholinergic neurons. Defects in this gene can cause sialidosis, a lysosomal storage disease. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2010]

SLC44A4 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=0.004440546).

BP6

Variant 6-31874821-T-A is Benign according to our data. Variant chr6-31874821-T-A is described in ClinVar as [Benign]. Clinvar id is 1266965.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SLC44A4	NM_025257.3 linkuse as main transcript	c.368A>T	p.Asp123Val	missense_variant	6/21	ENST00000229729.11	NP_079533.2
SLC44A4	NM_001178045.2 linkuse as main transcript	c.140A>T	p.Asp47Val	missense_variant	6/21		NP_001171516.1
SLC44A4	NM_001178044.2 linkuse as main transcript	c.342+108A>T		intron_variant			NP_001171515.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC44A4	ENST00000229729.11 linkuse as main transcript	c.368A>T	p.Asp123Val	missense_variant	6/21	1	NM_025257.3	ENSP00000229729	P1	Q53GD3-1

Frequencies

GnomAD3 genomes

AF:

0.114

AC:

17290

AN:

151504

Hom.:

1324

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0243

Gnomad AMI

AF:

0.192

Gnomad AMR

AF:

0.172

Gnomad ASJ

AF:

0.253

Gnomad EAS

AF:

0.110

Gnomad SAS

AF:

0.0879

Gnomad FIN

AF:

0.109

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.150

Gnomad OTH

AF:

0.108

GnomAD3 exomes

AF:

0.150

AC:

37178

AN:

247650

Hom.:

3267

AF XY:

0.148

AC XY:

19852

AN XY:

133960

show subpopulations

Gnomad AFR exome

AF:

0.0212

Gnomad AMR exome

AF:

0.233

Gnomad ASJ exome

AF:

0.262

Gnomad EAS exome

AF:

0.116

Gnomad SAS exome

AF:

0.0963

Gnomad FIN exome

AF:

0.116

Gnomad NFE exome

AF:

0.161

Gnomad OTH exome

AF:

0.140

GnomAD4 exome

AF:

0.136

AC:

198331

AN:

1460814

Hom.:

14785

Cov.:

AF XY:

0.136

AC XY:

98785

AN XY:

726770

show subpopulations

Gnomad4 AFR exome

AF:

0.0187

Gnomad4 AMR exome

AF:

0.226

Gnomad4 ASJ exome

AF:

0.239

Gnomad4 EAS exome

AF:

0.127

Gnomad4 SAS exome

AF:

0.0931

Gnomad4 FIN exome

AF:

0.114

Gnomad4 NFE exome

AF:

0.139

Gnomad4 OTH exome

AF:

0.121

GnomAD4 genome

AF:

0.114

AC:

17302

AN:

151622

Hom.:

1324

Cov.:

AF XY:

0.112

AC XY:

8305

AN XY:

74128

show subpopulations

Gnomad4 AFR

AF:

0.0242

Gnomad4 AMR

AF:

0.173

Gnomad4 ASJ

AF:

0.253

Gnomad4 EAS

AF:

0.111

Gnomad4 SAS

AF:

0.0884

Gnomad4 FIN

AF:

0.109

Gnomad4 NFE

AF:

0.150

Gnomad4 OTH

AF:

0.109

Alfa

AF:

0.152

Hom.:

1357

Bravo

AF:

0.116

TwinsUK

AF:

0.143

AC:

529

ALSPAC

AF:

0.126

AC:

485

ESP6500AA

AF:

0.0288

AC:

127

ESP6500EA

AF:

0.154

AC:

1322

ExAC

AF:

0.147

AC:

17796

Asia WGS

AF:

0.0890

AC:

313

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	This variant is associated with the following publications: (PMID: 25629512) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.011

DANN

Benign

0.76

DEOGEN2

Benign

0.012

T;.;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.011

MetaRNN

Benign

0.0044

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.20

N;.;.

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.2

N;N;.

REVEL

Benign

0.045

Sift

Benign

0.14

T;T;.

Sift4G

Benign

0.18

T;T;.

Polyphen

0.0

B;.;.

Vest4

0.048

MPC

0.30

ClinPred

0.018

GERP RS

-9.7

Varity_R

0.096

gMVP

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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