15-80695589-G-A

Variant summary

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

The NM_021214.2(ABHD17C):c.160G>A(p.Ala54Thr) 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: 33)
  • Exomes 𝑓: 0.0000031 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ABHD17C NM_021214.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.12

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07602206).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABHD17C	NM_021214.2	c.160G>A	p.Ala54Thr	missense_variant	1/3	ENST00000258884.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABHD17C	ENST00000258884.5	c.160G>A	p.Ala54Thr	missense_variant	1/3	1	NM_021214.2	P1
ABHD17C	ENST00000558464.1	c.160G>A	p.Ala54Thr	missense_variant	1/3	1
ABHD17C	ENST00000560609.1	c.-116+15828G>A		intron_variant		4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000313 AC: 3 AN: 959514 Hom.: 0 Cov.: 32 AF XY: 0.00000219 AC XY: 1 AN XY: 456682

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000119

Gnomad4 OTH exome AF: 0.0000589

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

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

Sep 18, 2023

The c.160G>A (p.A54T) alteration is located in exon 1 (coding exon 1) of the ABHD17C gene. This alteration results from a G to A substitution at nucleotide position 160, causing the alanine (A) at amino acid position 54 to be replaced by a threonine (T). 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	0.084
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
Cadd	Benign	17
Dann	Benign	0.86
DEOGEN2	Benign	0.010	T;.
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.49	T;T
M_CAP	Uncertain	0.091	D
MetaRNN	Benign	0.076	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.55	N;N
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.36	N;N
REVEL	Benign	0.017
Sift	Benign	0.63	T;T
Sift4G	Benign	0.58	T;T
Polyphen		0.089	B;B
Vest4		0.082
MutPred		0.26		Gain of glycosylation at A54 (P = 0.0017);Gain of glycosylation at A54 (P = 0.0017);
MVP		0.39
MPC		1.4
ClinPred		0.21	T
GERP RS		1.8
Varity_R		0.063
gMVP		0.28

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

LitVar

Other links and lift over

dbSNP: rs1356243140; hg19: chr15-80987930;