15-80695785-G-C

Position:

• chr15-80695785-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_021214.2(ABHD17C):​c.356G>C​(p.Arg119Pro) variant causes a missense change. 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: 33)
• Consequence: ABHD17C NM_021214.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.19

Genes affected

ABHD17C (HGNC:26925): (abhydrolase domain containing 17C, depalmitoylase) Enables palmitoyl-(protein) hydrolase activity. Involved in protein depalmitoylation. Predicted to be located in postsynaptic density. Predicted to be active in endosome membrane; glutamatergic synapse; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.893

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABHD17C	NM_021214.2	c.356G>C	p.Arg119Pro	missense_variant	1/3	ENST00000258884.5	NP_067037.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABHD17C	ENST00000258884.5	c.356G>C	p.Arg119Pro	missense_variant	1/3	1	NM_021214.2	ENSP00000258884	P1
ABHD17C	ENST00000558464.1	c.356G>C	p.Arg119Pro	missense_variant	1/3	1		ENSP00000452778
ABHD17C	ENST00000560609.1	c.-116+16024G>C		intron_variant		4		ENSP00000453923

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

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

Oct 12, 2021

The c.356G>C (p.R119P) alteration is located in exon 1 (coding exon 1) of the ABHD17C gene. This alteration results from a G to C substitution at nucleotide position 356, causing the arginine (R) at amino acid position 119 to be replaced by a proline (P). 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	Pathogenic	0.71
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T;.
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Pathogenic	0.86	D
MetaRNN	Pathogenic	0.89	D;D
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	2.0	M;M
MutationTaster	Benign	0.99	D;D;D
PrimateAI	Pathogenic	0.95	D
PROVEAN	Pathogenic	-4.5	D;D
REVEL	Uncertain	0.48
Sift	Uncertain	0.0070	D;D
Sift4G	Uncertain	0.044	D;D
Polyphen		0.88	P;D
Vest4		0.75
MutPred		0.53		Loss of MoRF binding (P = 0.014);Loss of MoRF binding (P = 0.014);
MVP		0.85
MPC		3.1
ClinPred		0.99	D
GERP RS		4.4
Varity_R		0.86
gMVP		0.99

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: chr15-80988126;