20-63861608-C-T

Variant names:

• chr20-63861608-C-T
• rs754047152
• NM_080622.4:c.68C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_080622.4(ABHD16B):​c.68C>T​(p.Thr23Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000712 in 1,404,274 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T23S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: ABHD16B NM_080622.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17981708).

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.68C>T	p.Thr23Ile	missense	Exon 1 of 1	NP_542189.1	Q9H3Z7
	ABHD16B-AS1	NR_165198.1		n.2815G>A		non_coding_transcript_exon	Exon 2 of 2
	ABHD16B-AS1	NR_165312.1		n.3466G>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.68C>T	p.Thr23Ile	missense	Exon 1 of 1	ENSP00000358932.3	Q9H3Z7
	ENSG00000268858	ENST00000601296.3	TSL:6	n.3616G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000608 AC: 1 AN: 164550 AF XY: 0.00

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: 0.0000148

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.12e-7 AC: 1 AN: 1404274 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 694216

African (AFR) AF: 0.00 AC: 0 AN: 32032

American (AMR) AF: 0.00 AC: 0 AN: 37444

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25320

East Asian (EAS) AF: 0.00 AC: 0 AN: 36494

South Asian (SAS) AF: 0.00 AC: 0 AN: 80138

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43960

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1084876

Other (OTH) AF: 0.0000171 AC: 1 AN: 58314

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000874 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		1.2
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.044
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.32	B
Vest4		0.35
MutPred		0.48		Gain of sheet (P = 0.0061)
MVP		0.22
MPC		0.53
ClinPred		0.13	T
GERP RS		-2.9
PromoterAI		-0.017	Neutral
Varity_R		0.084
gMVP		0.38
Mutation Taster		=97/3	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: rs754047152; hg19: chr20-62492961;