NM_198147.3:c.1209G>C

Variant names:

• chr17-29562759-C-G
• NM_198147.3:c.1209G>C

Variant summary

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

The NM_198147.3(ABHD15):​c.1209G>C​(p.Trp403Cys) 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)
• Consequence: ABHD15 NM_198147.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.23
• Publications: 0 publications found

Genes affected

ABHD15 (HGNC:26971): (abhydrolase domain containing 15) Predicted to enable acylglycerol lipase activity and short-chain carboxylesterase activity. Predicted to be involved in cellular lipid metabolic process. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ABHD15-AS1 (HGNC:49685): (ABHD15 antisense RNA 1)

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, 0.83

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198147.3. 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
	ABHD15	NM_198147.3	MANE Select	c.1209G>C	p.Trp403Cys	missense	Exon 2 of 2	NP_937790.2	Q6UXT9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABHD15	ENST00000307201.5	TSL:1 MANE Select	c.1209G>C	p.Trp403Cys	missense	Exon 2 of 2	ENSP00000302657.3	Q6UXT9
	ABHD15-AS1	ENST00000581474.1	TSL:5	n.153+2060C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 77

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	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.51	D
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.029	D
MetaRNN	Pathogenic	0.83	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		7.2
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-7.3	D
REVEL	Uncertain	0.52
Sift	Uncertain	0.0040	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.95
MutPred		0.48		Gain of catalytic residue at H405 (P = 0.0455)
MVP		0.47
MPC		0.25
ClinPred		0.99	D
GERP RS		5.7
Varity_R		0.78
gMVP		0.90

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

Other links and lift over

hg19: chr17-27889777;