chr3-51970079-A-G

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001146314.2(ABHD14B):c.317T>C(p.Val106Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000344 in 1,455,432 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

ABHD14B
NM_001146314.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.60

Variant links:

Genes affected

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:

PCBP4 (HGNC:8652): (poly(rC) binding protein 4) This gene encodes a member of the KH-domain protein subfamily. Proteins of this subfamily, also referred to as alpha-CPs, bind to RNA with a specificity for C-rich pyrimidine regions. Alpha-CPs play important roles in post-transcriptional activities and have different cellular distributions. This gene is induced by the p53 tumor suppressor, and the encoded protein can suppress cell proliferation by inducing apoptosis and cell cycle arrest in G(2)-M. This gene's protein is found in the cytoplasm, yet it lacks the nuclear localization signals found in other subfamily members. Multiple alternatively spliced transcript variants have been described, but the full-length nature for only some has been determined. [provided by RefSeq, Jul 2008]

PCBP4 links:

ENSG00000272762 (HGNC:):

ENSG00000272762 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32651886).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABHD14B	NM_001146314.2 link	c.317T>C	p.Val106Ala	missense_variant	Exon 3 of 4	ENST00000361143.10	NP_001139786.1	Q96IU4-1V9HW87
ABHD14B	NM_032750.3 link	c.317T>C	p.Val106Ala	missense_variant	Exon 3 of 4		NP_116139.1	Q96IU4-1V9HW87
ABHD14B	NM_001254753.1 link	c.203T>C	p.Val68Ala	missense_variant	Exon 2 of 3		NP_001241682.1	Q96IU4-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABHD14B	ENST00000361143.10 link	c.317T>C	p.Val106Ala	missense_variant	Exon 3 of 4	1	NM_001146314.2	ENSP00000354841.5		Q96IU4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000406

AC:

AN:

246148

Hom.:

AF XY:

0.00000752

AC XY:

AN XY:

132976

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000901

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000344

AC:

AN:

1455432

Hom.:

Cov.:

AF XY:

0.00000691

AC XY:

AN XY:

723240

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:

0.00000451

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000286

Hom.:

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 15, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.317T>C (p.V106A) alteration is located in exon 3 (coding exon 2) of the ABHD14B gene. This alteration results from a T to C substitution at nucleotide position 317, causing the valine (V) at amino acid position 106 to be replaced by an alanine (A). 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

0.17

BayesDel_addAF

Benign

-0.053

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

T;.;T;T;T;T

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.73

.;T;.;.;T;T

M_CAP

Benign

0.029

MetaRNN

Benign

0.33

T;T;T;T;T;T

MetaSVM

Benign

-0.64

MutationAssessor

Benign

2.0

M;.;M;M;.;M

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-3.6

D;D;D;D;D;D

REVEL

Benign

0.13

Sift

Uncertain

0.018

D;D;D;D;D;D

Sift4G

Uncertain

0.030

D;D;D;D;D;D

Polyphen

0.92

P;.;P;P;D;P

Vest4

0.34

MutPred

0.58

Gain of disorder (P = 0.0509);.;Gain of disorder (P = 0.0509);Gain of disorder (P = 0.0509);Gain of disorder (P = 0.0509);Gain of disorder (P = 0.0509);

MVP

0.83

MPC

0.29

ClinPred

0.96

GERP RS

2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.80

gMVP

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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