Variant chr15-80695608-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021214.2(ABHD17C):c.179C>T(p.Ala60Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000312 in 1,153,058 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

ABHD17C
NM_021214.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0460

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 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=0.06992376).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABHD17C	NM_021214.2 linkuse as main transcript	c.179C>T	p.Ala60Val	missense_variant	1/3	ENST00000258884.5	NP_067037.1	Q6PCB6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ABHD17C	ENST00000258884.5 linkuse as main transcript	c.179C>T	p.Ala60Val	missense_variant	1/3	1	NM_021214.2	ENSP00000258884.4	Q6PCB6-1
ABHD17C	ENST00000558464.1 linkuse as main transcript	c.179C>T	p.Ala60Val	missense_variant	1/3	1		ENSP00000452778.1	Q6PCB6-2
ABHD17C	ENST00000560609.1 linkuse as main transcript	c.-116+15847C>T		intron_variant		4		ENSP00000453923.1	H0YN98

Frequencies

GnomAD3 genomes

AF:

0.0000135

AC:

AN:

147814

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000244

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:

0.000113

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000338

AC:

AN:

1005244

Hom.:

Cov.:

AF XY:

0.0000231

AC XY:

AN XY:

475804

show subpopulations

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:

0.0000366

Gnomad4 OTH exome

AF:

0.0000532

GnomAD4 genome

AF:

0.0000135

AC:

AN:

147814

Hom.:

Cov.:

AF XY:

0.0000139

AC XY:

AN XY:

71992

show subpopulations

Gnomad4 AFR

AF:

0.0000244

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000113

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

Apr 13, 2022

The c.179C>T (p.A60V) 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 179, causing the alanine (A) at amino acid position 60 to be replaced by a valine (V). 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

0.10

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.56

CADD

Benign

9.7

DANN

Benign

0.95

DEOGEN2

Benign

0.014

T;.

Eigen

Benign

-0.99

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.0097

LIST_S2

Benign

0.45

T;T

M_CAP

Benign

0.032

MetaRNN

Benign

0.070

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

N;N

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.37

N;N

REVEL

Benign

0.013

Sift

Benign

0.39

T;T

Sift4G

Benign

0.37

T;T

Polyphen

0.32

B;B

Vest4

0.064

MutPred

0.19

Loss of glycosylation at P59 (P = 0.0725);Loss of glycosylation at P59 (P = 0.0725);

MVP

0.43

MPC

1.4

ClinPred

0.13

GERP RS

2.9

Varity_R

0.045

gMVP

0.31

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