4-128009156-C-A

Variant names:

• chr4-128009156-C-A
• NM_001358451.3:c.407C>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001358451.3(ABHD18):​c.407C>A​(p.Ala136Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ABHD18 NM_001358451.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.26
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.821

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001358451.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABHD18	NM_001358451.3	MANE Select	c.407C>A	p.Ala136Asp	missense	Exon 6 of 13	NP_001345380.1	A0A2R8YEZ0
	ABHD18	NM_001358454.3		c.452C>A	p.Ala151Asp	missense	Exon 7 of 14	NP_001345383.1
	ABHD18	NM_001366043.1		c.407C>A	p.Ala136Asp	missense	Exon 6 of 12	NP_001352972.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABHD18	ENST00000645843.2	MANE Select	c.407C>A	p.Ala136Asp	missense	Exon 6 of 13	ENSP00000496010.1	A0A2R8YEZ0
	ABHD18	ENST00000444616.5	TSL:5	c.407C>A	p.Ala136Asp	missense	Exon 6 of 11	ENSP00000397229.1	Q0P651-1
	ABHD18	ENST00000388795.10	TSL:5	n.*165C>A		non_coding_transcript_exon	Exon 6 of 13	ENSP00000373447.6	B7WP89

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1371324 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 679438

African (AFR) AF: 0.00 AC: 0 AN: 28012

American (AMR) AF: 0.00 AC: 0 AN: 22054

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22890

East Asian (EAS) AF: 0.00 AC: 0 AN: 35300

South Asian (SAS) AF: 0.00 AC: 0 AN: 67684

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5506

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1081038

Other (OTH) AF: 0.00 AC: 0 AN: 56442

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Pathogenic	0.41	D
BayesDel_noAF	Pathogenic	0.35
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.044	T
Eigen	Uncertain	0.64
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.0075	T
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-0.59	T
PhyloP100		7.3
PROVEAN	Uncertain	-3.2	D
REVEL	Pathogenic	0.72
Sift	Benign	0.059	T
Sift4G	Benign	0.14	T
Polyphen		0.98	D
Vest4		0.93
MutPred		0.61		Loss of helix (P = 0.0104)
MVP		0.69
MPC		0.41
ClinPred		0.99	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.51
gMVP		0.85
Mutation Taster		=29/71	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr4-128930311;