9-71866798-C-G

Variant names:

• chr9-71866798-C-G
• NM_001025780.3:c.856G>C
• ABHD17B p.Val286Leu

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_016014.4(ABHD17B):​c.855+1G>C variant causes a splice donor, intron 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. 1/1 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ABHD17B NM_016014.4 splice_donor, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.01
• Publications: 0 publications found

Genes affected

ABHD17B (HGNC:24278): (abhydrolase domain containing 17B, depalmitoylase) Enables palmitoyl-(protein) hydrolase activity. Involved in protein depalmitoylation. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016014.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABHD17B	NM_001025780.3	MANE Select	c.856G>C	p.Val286Leu	missense	Exon 4 of 4	NP_001020951.1	Q5VST6-1
	ABHD17B	NM_016014.4		c.855+1G>C		splice_donor intron	N/A	NP_057098.2	Q5VST6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABHD17B	ENST00000333421.7	TSL:1 MANE Select	c.856G>C	p.Val286Leu	missense	Exon 4 of 4	ENSP00000330222.6	Q5VST6-1
	ABHD17B	ENST00000377041.6	TSL:1	c.855+1G>C		splice_donor intron	N/A	ENSP00000366240.2	Q5VST6-2
	ABHD17B	ENST00000860588.1		c.856G>C	p.Val286Leu	missense	Exon 5 of 5	ENSP00000530647.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Pathogenic	0.40	D
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	23
DANN	Uncertain	1.0
Eigen	Benign	-0.062
Eigen_PC	Benign	0.14
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Benign	0.053	D
PhyloP100		3.0
Varity_R		0.11
Mutation Taster		=0/100	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.91		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.91		Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr9-74481714;