rs757473420

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_016006.6(ABHD5):c.14A>C(p.Glu5Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000274 in 1,566,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E5K) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

ABHD5
NM_016006.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 0.353

Publications

2 publications found

Variant links:

Genes affected

ABHD5 (HGNC:21396): (abhydrolase domain containing 5, lysophosphatidic acid acyltransferase) The protein encoded by this gene belongs to a large family of proteins defined by an alpha/beta hydrolase fold, and contains three sequence motifs that correspond to a catalytic triad found in the esterase/lipase/thioesterase subfamily. It differs from other members of this subfamily in that its putative catalytic triad contains an asparagine instead of the serine residue. Mutations in this gene have been associated with Chanarin-Dorfman syndrome, a triglyceride storage disease with impaired long-chain fatty acid oxidation. [provided by RefSeq, Jul 2008]

ABHD5 links:

ANO10 (HGNC:25519): (anoctamin 10) The transmembrane protein encoded by this gene belongs to the anoctamin family of calcium-activated chloride channels, also known as the transmembrane 16 family. The encoded protein contains eight transmembrane domains with cytosolic N- and C-termini. Defects in this gene may cause autosomal recessive spinocerebellar ataxia-10. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2016]

ANO10 Gene-Disease associations (from GenCC):

autosomal recessive spinocerebellar ataxia 10
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet

ANO10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.17974874).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016006.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ABHD5	NM_016006.6	MANE Select	c.14A>C	p.Glu5Ala	missense	Exon 1 of 7	NP_057090.2
ABHD5	NM_001355186.2		c.14A>C	p.Glu5Ala	missense	Exon 1 of 8	NP_001342115.1	Q8WTS1
ABHD5	NM_001365650.1		c.14A>C	p.Glu5Ala	missense	Exon 1 of 6	NP_001352579.1	A0A2U3TZT9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ABHD5	ENST00000644371.2	MANE Select	c.14A>C	p.Glu5Ala	missense	Exon 1 of 7	ENSP00000495778.1	Q8WTS1
ABHD5	ENST00000458276.7	TSL:1	c.14A>C	p.Glu5Ala	missense	Exon 1 of 6	ENSP00000390849.3	A0A2U3TZT9
ABHD5	ENST00000967519.1		c.14A>C	p.Glu5Ala	missense	Exon 1 of 8	ENSP00000637578.1

Frequencies

GnomAD3 genomes

AF:

0.0000266

AC:

AN:

150166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000591

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000803

AC:

AN:

199244

AF XY:

0.0000809

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000117

Gnomad EAS exome

AF:

0.0000810

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000334

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000275

AC:

AN:

1416796

Hom.:

Cov.:

AF XY:

0.0000340

AC XY:

AN XY:

704918

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29340

American (AMR)

AF:

0.00

AC:

AN:

39874

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24772

East Asian (EAS)

AF:

0.0000290

AC:

AN:

34430

South Asian (SAS)

AF:

0.000171

AC:

AN:

81994

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49926

Middle Eastern (MID)

AF:

0.000357

AC:

AN:

5610

European-Non Finnish (NFE)

AF:

0.0000110

AC:

AN:

1092476

Other (OTH)

AF:

0.000171

AC:

AN:

58374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

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:

0.0000266

AC:

AN:

150166

Hom.:

Cov.:

AF XY:

0.0000410

AC XY:

AN XY:

73192

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40608

American (AMR)

AF:

0.00

AC:

AN:

15084

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3452

East Asian (EAS)

AF:

0.00

AC:

AN:

5038

South Asian (SAS)

AF:

0.00

AC:

AN:

4732

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10310

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.0000591

AC:

AN:

67664

Other (OTH)

AF:

0.00

AC:

AN:

2066

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.0000500

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000748

AC:

Asia WGS

AF:

0.000579

AC:

AN:

3466

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.10

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.10

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.69

M_CAP

Pathogenic

0.69

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.80

MutationAssessor

Benign

0.0

PhyloP100

0.35

PrimateAI

Uncertain

0.73

PROVEAN

Benign

0.45

REVEL

Uncertain

0.42

Sift

Benign

0.13

Sift4G

Benign

0.38

Polyphen

0.019

Vest4

0.34

MutPred

0.13

Gain of helix (P = 0.0496)

MVP

0.75

MPC

0.16

ClinPred

0.047

GERP RS

3.0

PromoterAI

-0.029

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.53

Mutation Taster

=80/20

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over