Variant 3-51975203-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015407.5(ABHD14A):c.68C>G(p.Pro23Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000935 in 1,262,462 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000087 ( 0 hom. )

Consequence

ABHD14A
NM_015407.5 missense, splice_region

Scores

Splicing: ADA: 0.0002279

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.517

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08563501).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABHD14A	NM_015407.5 linkuse as main transcript	c.68C>G	p.Pro23Arg	missense_variant, splice_region_variant	1/5	ENST00000273596.8	NP_056222.2
ABHD14A-ACY1	NM_001316331.2 linkuse as main transcript	c.-78C>G		splice_region_variant, 5_prime_UTR_variant	1/17		NP_001303260.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABHD14A	ENST00000273596.8 linkuse as main transcript	c.68C>G	p.Pro23Arg	missense_variant, splice_region_variant	1/5	1	NM_015407.5	ENSP00000273596	P1

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

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:

0.000103

Gnomad OTH

AF:

0.000479

GnomAD4 exome

AF:

0.0000874

AC:

AN:

1110354

Hom.:

Cov.:

AF XY:

0.0000945

AC XY:

AN XY:

529068

show subpopulations

Gnomad4 AFR exome

AF:

0.0000866

Gnomad4 AMR exome

AF:

0.000221

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000666

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000898

Gnomad4 OTH exome

AF:

0.000157

GnomAD4 genome

AF:

0.000138

AC:

AN:

152108

Hom.:

Cov.:

AF XY:

0.000162

AC XY:

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.000589

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.000479

Bravo

AF:

0.000147

ExAC

AF:

0.0000130

AC:

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

Apr 12, 2022

The c.68C>G (p.P23R) alteration is located in exon 1 (coding exon 1) of the ABHD14A gene. This alteration results from a C to G substitution at nucleotide position 68, causing the proline (P) at amino acid position 23 to be replaced by an arginine (R). 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

0.046

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

7.6

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0027

T;.;.;.

Eigen

Benign

-0.90

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.60

T;T;T;T

M_CAP

Benign

0.026

MetaRNN

Benign

0.086

T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.41

N;.;.;.

MutationTaster

Benign

1.0

D;N;N;N;D

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.65

N;D;N;.

REVEL

Benign

0.026

Sift

Uncertain

0.021

D;D;D;.

Sift4G

Uncertain

0.030

D;D;D;.

Polyphen

0.0060

B;.;B;.

Vest4

0.13

MutPred

0.55

Gain of MoRF binding (P = 0.0214);Gain of MoRF binding (P = 0.0214);Gain of MoRF binding (P = 0.0214);Gain of MoRF binding (P = 0.0214);

MVP

0.42

MPC

0.17

ClinPred

0.15

GERP RS

0.98

Varity_R

0.051

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00023

dbscSNV1_RF

Benign

0.11

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

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