Variant 15-80695604-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_021214.2(ABHD17C):c.175C>T(p.Pro59Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000482 in 1,139,718 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00051 ( 1 hom. )

Consequence

ABHD17C
NM_021214.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0300

Variant links:

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]

ABHD17C links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.061148554).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABHD17C	NM_021214.2 linkuse as main transcript	c.175C>T	p.Pro59Ser	missense_variant	1/3	ENST00000258884.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABHD17C	ENST00000258884.5 linkuse as main transcript	c.175C>T	p.Pro59Ser	missense_variant	1/3	1	NM_021214.2	P1	Q6PCB6-1
ABHD17C	ENST00000558464.1 linkuse as main transcript	c.175C>T	p.Pro59Ser	missense_variant	1/3	1			Q6PCB6-2
ABHD17C	ENST00000560609.1 linkuse as main transcript	c.-116+15843C>T		intron_variant		4

Frequencies

GnomAD3 genomes

AF:

0.000264

AC:

AN:

147784

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000171

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000481

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000514

AC:

510

AN:

991934

Hom.:

Cov.:

AF XY:

0.000516

AC XY:

242

AN XY:

469204

show subpopulations

Gnomad4 AFR exome

AF:

0.0000514

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:

0.000582

Gnomad4 OTH exome

AF:

0.000164

GnomAD4 genome

AF:

0.000264

AC:

AN:

147784

Hom.:

Cov.:

AF XY:

0.000208

AC XY:

AN XY:

71980

show subpopulations

Gnomad4 AFR

AF:

0.000171

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000481

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.000272

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 17, 2022

The c.175C>T (p.P59S) 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 175, causing the proline (P) at amino acid position 59 to be replaced by a serine (S). 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

0.069

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.69

Cadd

Benign

Dann

Benign

0.90

DEOGEN2

Benign

0.016

T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.41

T;T

M_CAP

Benign

0.054

MetaRNN

Benign

0.061

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-1.5

N;N

REVEL

Benign

0.086

Sift

Benign

0.18

T;T

Sift4G

Benign

0.12

T;T

Polyphen

0.028

B;B

Vest4

0.069

MVP

0.10

MPC

1.4

ClinPred

0.078

GERP RS

-7.6

Varity_R

0.048

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over