20-63861682-C-T

Variant names:

• chr20-63861682-C-T
• rs965671960
• NM_080622.4:c.142C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_080622.4(ABHD16B):​c.142C>T​(p.Arg48Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000444 in 1,530,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R48Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000043 (0 hom.)
• Consequence: ABHD16B NM_080622.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0950
• Publications: 0 publications found

Genes affected

ABHD16B (HGNC:16128): (abhydrolase domain containing 16B) Predicted to enable acylglycerol lipase activity; palmitoyl-(protein) hydrolase activity; and phospholipase activity. Predicted to be involved in monoacylglycerol catabolic process and phosphatidylserine catabolic process. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000268858 (HGNC:58392):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34963447).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080622.4. 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
	ABHD16B	NM_080622.4	MANE Select	c.142C>T	p.Arg48Trp	missense	Exon 1 of 1	NP_542189.1	Q9H3Z7
	ABHD16B-AS1	NR_165198.1		n.2741G>A		non_coding_transcript_exon	Exon 2 of 2
	ABHD16B-AS1	NR_165312.1		n.3392G>A		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABHD16B	ENST00000369916.5	TSL:6 MANE Select	c.142C>T	p.Arg48Trp	missense	Exon 1 of 1	ENSP00000358932.3	Q9H3Z7
	ENSG00000268858	ENST00000601296.3	TSL:6	n.3542G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.0000593 AC: 9 AN: 151870 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000725

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: 0.0000883

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000306 AC: 4 AN: 130778 AF XY: 0.0000140

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000800

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000428 AC: 59 AN: 1378208 Hom.: 0 Cov.: 32 AF XY: 0.0000456 AC XY: 31 AN XY: 680160

African (AFR) AF: 0.0000327 AC: 1 AN: 30554

American (AMR) AF: 0.00 AC: 0 AN: 35116

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24736

East Asian (EAS) AF: 0.00 AC: 0 AN: 34820

South Asian (SAS) AF: 0.00 AC: 0 AN: 78836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37510

Middle Eastern (MID) AF: 0.000182 AC: 1 AN: 5504

European-Non Finnish (NFE) AF: 0.0000494 AC: 53 AN: 1073800

Other (OTH) AF: 0.0000698 AC: 4 AN: 57332

GnomAD4 genome AF: 0.0000593 AC: 9 AN: 151870 Hom.: 0 Cov.: 31 AF XY: 0.0000674 AC XY: 5 AN XY: 74212

African (AFR) AF: 0.0000725 AC: 3 AN: 41390

American (AMR) AF: 0.00 AC: 0 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10494

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000883 AC: 6 AN: 67944

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000234 Hom.: 0

Bravo AF: 0.0000567

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.070
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.71	T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.095
PrimateAI	Pathogenic	0.89	D
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.21
Sift	Benign	0.030	D
Sift4G	Uncertain	0.055	T
Polyphen		1.0	D
Vest4		0.43
MutPred		0.50		Loss of disorder (P = 0.0099)
MVP		0.49
MPC		1.3
ClinPred		0.36	T
GERP RS		4.3
PromoterAI		0.092	Neutral
Varity_R		0.064
gMVP		0.55
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs965671960; hg19: chr20-62493035; COSMIC: COSV53861597; COSMIC: COSV53861597;