Variant 2-27212345-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000380171(ATRAID):c.-24A>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000523 in 1,549,694 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000020 ( 1 hom. )

Consequence

ATRAID
ENST00000380171 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.15

Variant links:

Genes affected

ATRAID (HGNC:24090): (all-trans retinoic acid induced differentiation factor) This gene is thought to be involved in apoptosis, and may also be involved in hematopoietic development and differentiation. The use of alternative splice sites and promotors result in multiple transcript variants encoding different isoforms.[provided by RefSeq, Dec 2009]

ATRAID links:

SLC5A6 (HGNC:11041): (solute carrier family 5 member 6) Enables biotin transmembrane transporter activity and pantothenate transmembrane transporter activity. Involved in anion transmembrane transport and transport across blood-brain barrier. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC5A6 links:

ATRAID (HGNC:):

ATRAID links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.016306043).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATRAID	NM_001170795.4 linkuse as main transcript	c.-24A>T		5_prime_UTR_premature_start_codon_gain_variant	1/7	ENST00000380171.9	NP_001164266.1	Q6UW56-1
ATRAID	NM_001170795.4 linkuse as main transcript	c.-24A>T		5_prime_UTR_variant	1/7	ENST00000380171.9	NP_001164266.1	Q6UW56-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATRAID	ENST00000380171 linkuse as main transcript	c.-24A>T		5_prime_UTR_premature_start_codon_gain_variant	1/7	1	NM_001170795.4	ENSP00000369518.4		Q6UW56-1
ATRAID	ENST00000380171 linkuse as main transcript	c.-24A>T		5_prime_UTR_variant	1/7	1	NM_001170795.4	ENSP00000369518.4		Q6UW56-1

Frequencies

GnomAD3 genomes

AF:

0.000309

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00109

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.0000198

AC:

AN:

151218

Hom.:

AF XY:

0.0000248

AC XY:

AN XY:

80752

show subpopulations

Gnomad AFR exome

AF:

0.000256

Gnomad AMR exome

AF:

0.0000407

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000200

AC:

AN:

1397352

Hom.:

Cov.:

AF XY:

0.0000189

AC XY:

AN XY:

689168

show subpopulations

Gnomad4 AFR exome

AF:

0.000697

Gnomad4 AMR exome

AF:

0.0000281

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000691

GnomAD4 genome

AF:

0.000348

AC:

AN:

152342

Hom.:

Cov.:

AF XY:

0.000362

AC XY:

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.00123

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000946

Bravo

AF:

0.000287

ExAC

AF:

0.0000472

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 15, 2023

The c.142A>T (p.S48C) alteration is located in exon 1 (coding exon 1) of the ATRAID gene. This alteration results from a A to T substitution at nucleotide position 142, causing the serine (S) at amino acid position 48 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.058

DANN

Benign

0.75

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.0060

LIST_S2

Benign

0.34

.;T

M_CAP

Benign

0.0052

MetaRNN

Benign

0.016

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.55

PROVEAN

Benign

0.35

N;.

REVEL

Benign

0.054

Sift

Benign

0.14

T;.

Sift4G

Benign

0.10

T;T

Polyphen

0.0

B;B

Vest4

0.095

MVP

0.099

MPC

0.069

ClinPred

0.052

GERP RS

-10

gMVP

0.28

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