14-22606470-C-A

Position:

• chr14-22606470-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000428304.7(ABHD4):​c.689C>A​(p.Ala230Glu) 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. 13/21 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)
• Consequence: ABHD4 ENST00000428304.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.47

Genes affected

ABHD4 (HGNC:20154): (abhydrolase domain containing 4, N-acyl phospholipase B) Predicted to enable lysophosphatidic acid acyltransferase activity and lysophospholipase activity. Predicted to be involved in N-acylphosphatidylethanolamine metabolic process; lipid homeostasis; and phosphatidic acid biosynthetic process. Predicted to act upstream of or within N-acylethanolamine metabolic process. Predicted to be located in endoplasmic reticulum membrane. Predicted to be active in lipid droplet and mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ABHD4 (HGNC:):

ACMG classification

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=0.1658591).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABHD4	NM_022060.3	c.689C>A	p.Ala230Glu	missense_variant	5/7	ENST00000428304.7	NP_071343.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABHD4	ENST00000428304.7	c.689C>A	p.Ala230Glu	missense_variant	5/7	1	NM_022060.3	ENSP00000414558.2
ABHD4	ENST00000216327.10	c.*3+2380C>A		intron_variant		5		ENSP00000216327.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 21, 2024

The c.689C>A (p.A230E) alteration is located in exon 5 (coding exon 5) of the ABHD4 gene. This alteration results from a C to A substitution at nucleotide position 689, causing the alanine (A) at amino acid position 230 to be replaced by a glutamic acid (E). 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	0.18
BayesDel_addAF	Uncertain	0.021	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.047	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.026
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	-0.010	N
MutationTaster	Benign	0.83	N
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.21
Sift	Benign	0.23	T
Sift4G	Benign	0.47	T
Polyphen		0.016	B
Vest4		0.21
MutPred		0.56		Gain of disorder (P = 0.0269);
MVP		0.81
MPC		0.19
ClinPred		0.70	D
GERP RS		5.4
Varity_R		0.21
gMVP		0.87

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-23075376;