4-128028605-C-T

Position:

• chr4-128028605-C-T

Variant summary

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

The NM_001358451.3(ABHD18):​c.932C>T​(p.Pro311Leu) 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. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ABHD18 NM_001358451.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.599

Genes affected

ABHD18 (HGNC:26111): (abhydrolase domain containing 18) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

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=0.11016762).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABHD18	NM_001358451.3	c.932C>T	p.Pro311Leu	missense_variant	11/13	ENST00000645843.2	NP_001345380.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABHD18	ENST00000645843.2	c.932C>T	p.Pro311Leu	missense_variant	11/13		NM_001358451.3	ENSP00000496010.1
ABHD18	ENST00000444616.5	c.830C>T	p.Pro277Leu	missense_variant	10/11	5		ENSP00000397229.1
ABHD18	ENST00000388795.10	n.*690C>T		non_coding_transcript_exon_variant	11/13	5		ENSP00000373447.6
ABHD18	ENST00000388795.10	n.*690C>T		3_prime_UTR_variant	11/13	5		ENSP00000373447.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Apr 13, 2022

The c.830C>T (p.P277L) alteration is located in exon 10 (coding exon 9) of the ABHD18 gene. This alteration results from a C to T substitution at nucleotide position 830, causing the proline (P) at amino acid position 277 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	0.070
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	14
DANN	Benign	0.86
DEOGEN2	Benign	0.0027	T;.;T;T;.
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.82	T;T;.;T;T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.11	T;T;T;T;T
MetaSVM	Benign	-1.0	T
PROVEAN	Benign	-0.91	N;.;N;N;.
REVEL	Benign	0.042
Sift	Benign	0.29	T;.;T;T;.
Sift4G	Benign	0.28	T;.;T;T;T
Polyphen		0.014	B;.;B;B;.
Vest4		0.22
MutPred		0.47		Gain of helix (P = 0.005);.;Gain of helix (P = 0.005);.;.;
MVP		0.44
MPC		0.13
ClinPred		0.22	T
GERP RS		3.8
Varity_R		0.038
gMVP		0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr4-128949760;