Genetic Variant ATRAID:c.-38C>T (chr2-27212331-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_001170795.4(ATRAID):c.-38C>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 0.0000245 in 1,549,352 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

ATRAID
NM_001170795.4 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0780

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:

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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=0.02432698).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ATRAID	NM_001170795.4 link	c.-38C>T	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 7	ENST00000380171.9	NP_001164266.1	Q6UW56-1
ATRAID	NM_001170795.4 link	c.-38C>T	5_prime_UTR_variant	Exon 1 of 7	ENST00000380171.9	NP_001164266.1	Q6UW56-1
SLC5A6	NM_021095.4 link	c.-519G>A	upstream_gene_variant		ENST00000310574.8	NP_066918.2	Q9Y289Q9HD19

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ATRAID	ENST00000380171 link	c.-38C>T	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 7	1	NM_001170795.4	ENSP00000369518.4	Q6UW56-1
ATRAID	ENST00000380171 link	c.-38C>T	5_prime_UTR_variant	Exon 1 of 7	1	NM_001170795.4	ENSP00000369518.4	Q6UW56-1
SLC5A6	ENST00000310574.8 link	c.-519G>A	upstream_gene_variant		1	NM_021095.4	ENSP00000310208.3	Q9Y289

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000289

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000134

AC:

AN:

149492

Hom.:

AF XY:

0.0000250

AC XY:

AN XY:

80112

show subpopulations

Gnomad AFR exome

AF:

0.000266

Gnomad AMR exome

AF:

0.00

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:

0.0000129

AC:

AN:

1397030

Hom.:

Cov.:

AF XY:

0.0000145

AC XY:

AN XY:

688924

show subpopulations

Gnomad4 AFR exome

AF:

0.000253

Gnomad4 AMR exome

AF:

0.000141

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:

0.00000371

Gnomad4 OTH exome

AF:

0.0000173

GnomAD4 genome

AF:

0.000131

AC:

AN:

152322

Hom.:

Cov.:

AF XY:

0.000174

AC XY:

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000945

ExAC

AF:

0.0000362

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 27, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.128C>T (p.P43L) alteration is located in exon 1 (coding exon 1) of the ATRAID gene. This alteration results from a C to T substitution at nucleotide position 128, causing the proline (P) at amino acid position 43 to be replaced by a leucine (L). 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

-0.54

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.96

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.39

.;T

M_CAP

Benign

0.0085

MetaRNN

Benign

0.024

T;T

MetaSVM

Benign

-1.1

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.43

N;.

REVEL

Benign

0.065

Sift

Benign

0.42

T;.

Sift4G

Uncertain

0.030

D;D

Polyphen

0.0

B;B

Vest4

0.048

MVP

0.12

MPC

0.068

ClinPred

0.45

GERP RS

0.14

gMVP

0.30

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