2-27212381-G-C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001170795.4(ATRAID):c.13G>C(p.Asp5His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000429 in 1,398,264 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D5Y) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000043 ( 0 hom. )

Consequence

ATRAID
NM_001170795.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.229

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

neurodegeneration, infantile-onset, biotin-responsive
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, PanelApp Australia
peripheral motor neuropathy, childhood-onset, biotin-responsive
Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia
inherited neurodegenerative disorder
Inheritance: AR Classification: MODERATE Submitted by: Illumina

SLC5A6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.064434975).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001170795.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATRAID	NM_001170795.4	MANE Select	c.13G>C	p.Asp5His	missense	Exon 1 of 7	NP_001164266.1	Q6UW56-1
ATRAID	NM_016085.5		c.-302G>C		5_prime_UTR	Exon 1 of 7	NP_057169.2
SLC5A6	NM_021095.4	MANE Select	c.-569C>G		upstream_gene	N/A	NP_066918.2	Q9Y289

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATRAID	ENST00000380171.9	TSL:1 MANE Select	c.13G>C	p.Asp5His	missense	Exon 1 of 7	ENSP00000369518.4	Q6UW56-1
ATRAID	ENST00000405489.7	TSL:1	c.-302G>C		5_prime_UTR	Exon 1 of 7	ENSP00000384033.3	Q6UW56-2
ATRAID	ENST00000892973.1		c.13G>C	p.Asp5His	missense	Exon 1 of 7	ENSP00000563032.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000429

AC:

AN:

1398264

Hom.:

Cov.:

AF XY:

0.00000725

AC XY:

AN XY:

689786

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31540

American (AMR)

AF:

0.00

AC:

AN:

35694

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25138

East Asian (EAS)

AF:

0.00

AC:

AN:

35826

South Asian (SAS)

AF:

0.0000126

AC:

AN:

79198

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48486

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5614

European-Non Finnish (NFE)

AF:

0.00000463

AC:

AN:

1078796

Other (OTH)

AF:

0.00

AC:

AN:

57972

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.533

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.66

CADD

Benign

5.4

(source)

DANN

Benign

0.74

DEOGEN2

Benign

0.0018

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.22

M_CAP

Benign

0.0064

MetaRNN

Benign

0.064

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

-0.23

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.25

REVEL

Benign

0.0070

Sift

Benign

0.089

Sift4G

Benign

0.092

Polyphen

0.011

Vest4

0.083

MutPred

0.18

Loss of ubiquitination at K55 (P = 0.0247)

MVP

0.20

MPC

0.099

ClinPred

0.085

GERP RS

2.2

PromoterAI

-0.081

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.042

gMVP

0.35

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over