chr3-51969524-G-C

Variant names:

• chr3-51969524-G-C
• rs149746591
• NM_001146314.2:c.535C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001146314.2(ABHD14B):​c.535C>G​(p.Arg179Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ABHD14B NM_001146314.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.60

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]

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]

ENSG00000272762 (HGNC:):

ACMG classification

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=0.3139299).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABHD14B	NM_001146314.2	c.535C>G	p.Arg179Gly	missense_variant	Exon 4 of 4	ENST00000361143.10	NP_001139786.1
ABHD14B	NM_032750.3	c.535C>G	p.Arg179Gly	missense_variant	Exon 4 of 4		NP_116139.1
ABHD14B	NM_001254753.1	c.421C>G	p.Arg141Gly	missense_variant	Exon 3 of 3		NP_001241682.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABHD14B	ENST00000361143.10	c.535C>G	p.Arg179Gly	missense_variant	Exon 4 of 4	1	NM_001146314.2	ENSP00000354841.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000402 AC: 1 AN: 249016 Hom.: 0 AF XY: 0.00000742 AC XY: 1 AN XY: 134798

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: 0.00

Gnomad OTH exome AF: 0.000163

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T;.;T;T;T
Eigen	Benign	0.17
Eigen_PC	Benign	0.12
FATHMM_MKL	Benign	0.66	D
LIST_S2	Uncertain	0.90	.;D;.;.;D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.31	T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Pathogenic	3.2	M;.;M;M;M
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-3.7	D;D;D;D;D
REVEL	Benign	0.13
Sift	Benign	0.067	T;T;T;T;T
Sift4G	Uncertain	0.038	D;D;D;D;D
Polyphen		0.92	P;.;P;P;P
Vest4		0.32
MutPred		0.47		Loss of helix (P = 0.0558);.;Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);
MVP		0.56
MPC		0.32
ClinPred		0.53	D
GERP RS		0.68
Varity_R		0.28
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

Other links and lift over

dbSNP: rs149746591; hg19: chr3-52003540;