3-51970082-G-A

Position:

chr3-51970082-G-A

Variant summary

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

The NM_001146314.2(ABHD14B):c.314C>T(p.Pro105Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000424 in 1,602,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000043 ( 0 hom. )

Consequence

ABHD14B
NM_001146314.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.89

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:

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=0.17775488).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABHD14B	NM_001146314.2 link	c.314C>T	p.Pro105Leu	missense_variant	3/4	ENST00000361143.10	NP_001139786.1	Q96IU4-1V9HW87
ABHD14B	NM_032750.3 link	c.314C>T	p.Pro105Leu	missense_variant	3/4		NP_116139.1	Q96IU4-1V9HW87
ABHD14B	NM_001254753.1 link	c.200C>T	p.Pro67Leu	missense_variant	2/3		NP_001241682.1	Q96IU4-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABHD14B	ENST00000361143.10 link	c.314C>T	p.Pro105Leu	missense_variant	3/4	1	NM_001146314.2	ENSP00000354841.5		Q96IU4-1

Frequencies

GnomAD3 genomes

AF:

0.0000333

AC:

AN:

150184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000300

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000290

AC:

AN:

241504

Hom.:

AF XY:

0.0000384

AC XY:

AN XY:

130348

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000554

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000434

AC:

AN:

1452548

Hom.:

Cov.:

AF XY:

0.0000333

AC XY:

AN XY:

721458

show subpopulations

Gnomad4 AFR exome

AF:

0.0000601

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:

0.0000542

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000333

AC:

AN:

150302

Hom.:

Cov.:

AF XY:

0.0000544

AC XY:

AN XY:

73540

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000300

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000275

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000165

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

Oct 01, 2024

The c.314C>T (p.P105L) alteration is located in exon 3 (coding exon 2) of the ABHD14B gene. This alteration results from a C to T substitution at nucleotide position 314, causing the proline (P) at amino acid position 105 to be replaced by a leucine (L). 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

-0.22

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.10

T;.;T;T;T;T

Eigen

Benign

-0.032

Eigen_PC

Benign

0.039

FATHMM_MKL

Benign

0.74

LIST_S2

Uncertain

0.87

.;D;.;.;T;D

M_CAP

Benign

0.037

MetaRNN

Benign

0.18

T;T;T;T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.95

L;.;L;L;.;L

PrimateAI

Benign

0.43

PROVEAN

Pathogenic

-4.8

D;D;D;D;D;D

REVEL

Benign

0.075

Sift

Benign

0.073

T;T;T;T;T;T

Sift4G

Benign

0.12

T;T;T;T;T;T

Polyphen

0.48

P;.;P;P;P;P

Vest4

0.28

MutPred

0.46

Loss of catalytic residue at P104 (P = 0.0195);.;Loss of catalytic residue at P104 (P = 0.0195);Loss of catalytic residue at P104 (P = 0.0195);Loss of catalytic residue at P104 (P = 0.0195);Loss of catalytic residue at P104 (P = 0.0195);

MVP

0.82

MPC

0.45

ClinPred

0.72

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.47

gMVP

0.64

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

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