2-27212393-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001170795.4(ATRAID):c.25C>T(p.Leu9Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,551,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/24 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000050 ( 0 hom. )

Consequence

ATRAID
NM_001170795.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.18

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: Uncertain_significance. The variant received 0 ACMG points.

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.25C>T	p.Leu9Phe	missense	Exon 1 of 7	NP_001164266.1	Q6UW56-1
ATRAID	NM_016085.5		c.-290C>T		5_prime_UTR	Exon 1 of 7	NP_057169.2
SLC5A6	NM_021095.4	MANE Select	c.-581G>A		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.25C>T	p.Leu9Phe	missense	Exon 1 of 7	ENSP00000369518.4	Q6UW56-1
ATRAID	ENST00000405489.7	TSL:1	c.-290C>T		5_prime_UTR	Exon 1 of 7	ENSP00000384033.3	Q6UW56-2
ATRAID	ENST00000892973.1		c.25C>T	p.Leu9Phe	missense	Exon 1 of 7	ENSP00000563032.1

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

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:

0.00

GnomAD2 exomes

AF:

0.0000259

AC:

AN:

154208

AF XY:

0.0000244

show subpopulations

Gnomad AFR exome

AF:

0.000490

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000500

AC:

AN:

1398720

Hom.:

Cov.:

AF XY:

0.00000290

AC XY:

AN XY:

690092

show subpopulations

African (AFR)

AF:

0.000127

AC:

AN:

31500

American (AMR)

AF:

0.00

AC:

AN:

35718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25138

East Asian (EAS)

AF:

0.00

AC:

AN:

35844

South Asian (SAS)

AF:

0.00

AC:

AN:

79180

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48516

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5650

European-Non Finnish (NFE)

AF:

0.00000278

AC:

AN:

1079186

Other (OTH)

AF:

0.00

AC:

AN:

57988

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

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

AF:

0.0000591

AC:

AN:

152350

Hom.:

Cov.:

AF XY:

0.0000940

AC XY:

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.000216

AC:

AN:

41596

American (AMR)

AF:

0.00

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5158

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68040

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000680

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.67

CADD

Benign

1.3

(source)

DANN

Benign

0.82

DEOGEN2

Benign

0.0013

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.30

M_CAP

Benign

0.0049

MetaRNN

Benign

0.014

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.34

PhyloP100

-2.2

PrimateAI

Uncertain

0.48

PROVEAN

Benign

-0.080

REVEL

Benign

0.015

Sift

Benign

0.10

Sift4G

Benign

0.73

Polyphen

0.0040

Vest4

0.032

MVP

0.095

MPC

0.070

ClinPred

0.014

GERP RS

-1.5

PromoterAI

0.013

Neutral

(source)

Varity_R

0.036

gMVP

0.22

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.22

Position offset: -6

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over