Variant 3-51980936-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_015407.5(ABHD14A):c.734G>C(p.Arg245Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ABHD14A
NM_015407.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.216

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:):

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:

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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=0.04444617).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABHD14A	NM_015407.5 linkuse as main transcript	c.734G>C	p.Arg245Pro	missense_variant	5/5	ENST00000273596.8	NP_056222.2
ABHD14A-ACY1	NM_001316331.2 linkuse as main transcript	c.252+2562G>C		intron_variant			NP_001303260.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABHD14A	ENST00000273596.8 linkuse as main transcript	c.734G>C	p.Arg245Pro	missense_variant	5/5	1	NM_015407.5	ENSP00000273596	P1
ABHD14B	ENST00000483233.5 linkuse as main transcript	c.-299+2265C>G		intron_variant		1		ENSP00000420065	P3	Q96IU4-1
ABHD14A	ENST00000491470.1 linkuse as main transcript	c.*7G>C		3_prime_UTR_variant	3/3	3		ENSP00000418824

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461826

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 16, 2023

The c.734G>C (p.R245P) alteration is located in exon 5 (coding exon 5) of the ABHD14A gene. This alteration results from a G to C substitution at nucleotide position 734, causing the arginine (R) at amino acid position 245 to be replaced by a proline (P). 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

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.096

DANN

Benign

0.62

DEOGEN2

Benign

0.0058

.;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.67

T;T

M_CAP

Benign

0.0052

MetaRNN

Benign

0.044

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-1.6

.;N

MutationTaster

Benign

0.99

N;N;N;N;N

PrimateAI

Benign

0.19

PROVEAN

Benign

-1.4

.;N

REVEL

Benign

0.061

Sift

Benign

0.60

.;T

Sift4G

Benign

0.32

T;T

Polyphen

0.0

.;B

Vest4

0.15

MutPred

0.47

.;Loss of MoRF binding (P = 0.0387);

MVP

0.085

MPC

0.23

ClinPred

0.047

GERP RS

-7.7

Varity_R

0.12

gMVP

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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