Variant 15-80695646-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.217C>T(p.Pro73Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000177 in 1,354,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

ABHD17C
NM_021214.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.225

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=0.09429988).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABHD17C	NM_021214.2 linkuse as main transcript	c.217C>T	p.Pro73Ser	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.217C>T	p.Pro73Ser	missense_variant	1/3	1	NM_021214.2	ENSP00000258884.4	Q6PCB6-1
ABHD17C	ENST00000558464.1 linkuse as main transcript	c.217C>T	p.Pro73Ser	missense_variant	1/3	1		ENSP00000452778.1	Q6PCB6-2
ABHD17C	ENST00000560609.1 linkuse as main transcript	c.-116+15885C>T		intron_variant		4		ENSP00000453923.1	H0YN98

Frequencies

GnomAD3 genomes

AF:

0.0000201

AC:

AN:

149460

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000174

AC:

AN:

1205236

Hom.:

Cov.:

AF XY:

0.0000240

AC XY:

AN XY:

583782

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:

0.000385

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000101

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000201

AC:

AN:

149570

Hom.:

Cov.:

AF XY:

0.0000274

AC XY:

AN XY:

73038

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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

Jun 28, 2024

The c.217C>T (p.P73S) 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 217, causing the proline (P) at amino acid position 73 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

0.065

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0048

T;.

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.089

LIST_S2

Benign

0.46

T;T

M_CAP

Uncertain

0.24

MetaRNN

Benign

0.094

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.11

N;N

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.25

N;N

REVEL

Benign

0.087

Sift

Benign

0.22

T;T

Sift4G

Benign

0.77

T;T

Polyphen

0.059

B;B

Vest4

0.18

MutPred

0.21

Gain of phosphorylation at P73 (P = 0.0343);Gain of phosphorylation at P73 (P = 0.0343);

MVP

0.40

MPC

1.4

ClinPred

0.12

GERP RS

3.5

Varity_R

0.071

gMVP

0.35

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