chr15-80695539-C-T

Position:

• chr15-80695539-C-T

Variant summary

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

The NM_021214.2(ABHD17C):​c.110C>T​(p.Pro37Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ABHD17C NM_021214.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.69

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABHD17C	NM_021214.2	c.110C>T	p.Pro37Leu	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.110C>T	p.Pro37Leu	missense_variant	1/3	1	NM_021214.2	ENSP00000258884.4
ABHD17C	ENST00000558464.1	c.110C>T	p.Pro37Leu	missense_variant	1/3	1		ENSP00000452778.1
ABHD17C	ENST00000560609.1	c.-116+15778C>T		intron_variant		4		ENSP00000453923.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1211370 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 597682

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: 0.00

Gnomad4 OTH exome AF: 0.00

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

Nov 25, 2024

The c.110C>T (p.P37L) alteration is located in exon 1 (coding exon 1) of the ABHD17C gene. This alteration results from a C to T substitution at nucleotide position 110, causing the proline (P) at amino acid position 37 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	Pathogenic	1.0
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.53	D;.
Eigen	Uncertain	0.26
Eigen_PC	Benign	0.095
FATHMM_MKL	Benign	0.46	N
LIST_S2	Pathogenic	0.99	D;D
M_CAP	Pathogenic	0.55	D
MetaRNN	Uncertain	0.70	D;D
MetaSVM	Benign	-0.38	T
MutationAssessor	Pathogenic	3.1	M;M
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-7.6	D;D
REVEL	Uncertain	0.36
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0010	D;D
Polyphen		1.0	D;D
Vest4		0.45
MutPred		0.59		Loss of glycosylation at P37 (P = 0.0075);Loss of glycosylation at P37 (P = 0.0075);
MVP		0.71
MPC		2.7
ClinPred		1.0	D
GERP RS		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
Varity_R		0.56
gMVP		0.81

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: rs1806961695; hg19: chr15-80987880;