rs1040643214

Variant names:

Variant summary

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

The NM_015407.5(ABHD14A):c.62T>G(p.Leu21Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000537 in 1,266,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000086 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000049 ( 0 hom. )

Consequence

ABHD14A
NM_015407.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0300

Publications

1 publications found

Variant links:

Genes affected

ABHD14A (HGNC:24538): (abhydrolase domain containing 14A) Predicted to enable hydrolase activity. Predicted to be integral component of membrane. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ABHD14A links:

ABHD14A-ACY1 (HGNC:38856): (ABHD14A-ACY1 readthrough) This locus represents naturally occurring read-through transcription between the neighboring abhydrolase domain containing 14A (ABHD14A) and aminoacylase 1 (ACY1) genes on chromosome 3. The read-through transcript encodes a protein that shares sequence identity with the downstream gene product but its N-terminal region is distinct due to the use of an alternate start codon relative to the upstream gene. [provided by RefSeq, Oct 2015]

ABHD14A-ACY1 links:

ABHD14B (HGNC:28235): (abhydrolase domain containing 14B) Enables hydrolase activity. Involved in positive regulation of transcription by RNA polymerase II. Located in cytosol; nucleolus; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ABHD14B 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=0.07076776).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015407.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABHD14A	NM_015407.5	MANE Select	c.62T>G	p.Leu21Trp	missense	Exon 1 of 5	NP_056222.2	Q9BUJ0
	ABHD14A-ACY1	NM_001316331.2		c.-84T>G		5_prime_UTR	Exon 1 of 17	NP_001303260.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ABHD14A	ENST00000273596.8	TSL:1 MANE Select	c.62T>G	p.Leu21Trp	missense	Exon 1 of 5	ENSP00000273596.3	Q9BUJ0
ABHD14A-ACY1	ENST00000463937.1	TSL:5	c.62T>G	p.Leu21Trp	missense	Exon 1 of 16	ENSP00000420487.1	C9JMV9
ABHD14B	ENST00000483233.5	TSL:1	c.-298-963A>C		intron	N/A	ENSP00000420065.1	Q96IU4-1

Frequencies

GnomAD3 genomes

AF:

0.0000855

AC:

AN:

152022

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000958

GnomAD2 exomes

AF:

0.00

AC:

AN:

3908

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

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:

0.0000493

AC:

AN:

1114868

Hom.:

Cov.:

AF XY:

0.0000414

AC XY:

AN XY:

531878

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23120

American (AMR)

AF:

0.000977

AC:

AN:

9212

Ashkenazi Jewish (ASJ)

AF:

0.00221

AC:

AN:

14960

East Asian (EAS)

AF:

0.00

AC:

AN:

26694

South Asian (SAS)

AF:

0.00

AC:

AN:

31468

European-Finnish (FIN)

AF:

0.00

AC:

AN:

23862

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3010

European-Non Finnish (NFE)

AF:

0.00000640

AC:

AN:

937648

Other (OTH)

AF:

0.000156

AC:

AN:

44894

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

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:

0.0000855

AC:

AN:

152022

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74276

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41416

American (AMR)

AF:

0.000393

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5156

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67954

Other (OTH)

AF:

0.000958

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

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:

0.000113

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

0.074

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.0019

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.096

LIST_S2

Benign

0.55

M_CAP

Benign

0.061

MetaRNN

Benign

0.071

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.69

PhyloP100

-0.030

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.39

REVEL

Benign

0.052

Sift

Uncertain

0.020

Sift4G

Uncertain

0.013

Polyphen

0.76

Vest4

0.20

MutPred

0.27

Loss of stability (P = 0.1044)

MVP

0.59

MPC

0.37

ClinPred

0.14

GERP RS

1.2

PromoterAI

-0.051

Neutral

(source)

Varity_R

0.055

gMVP

0.44

Mutation Taster

=97/3

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