6-31691667-C-T

Position:

• chr6-31691667-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_021160.3(ABHD16A):​c.755G>A​(p.Arg252Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000411 in 1,458,986 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: ABHD16A NM_021160.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.02

Genes affected

ABHD16A (HGNC:13921): (abhydrolase domain containing 16A, phospholipase) A cluster of genes, BAT1-BAT5, has been localized in the vicinity of the genes for tumor necrosis factor alpha and tumor necrosis factor beta. These genes are all within the human major histocompatibility complex class III region. The protein encoded by this gene is thought to be involved in some aspects of immunity. Alternatively spliced transcript variants have been described. [provided by RefSeq, Apr 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.825

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABHD16A	NM_021160.3	c.755G>A	p.Arg252Gln	missense_variant	9/20	ENST00000395952.8	NP_066983.1
ABHD16A	NM_001177515.2	c.656G>A	p.Arg219Gln	missense_variant	7/18		NP_001170986.1
ABHD16A	NR_033488.2	n.970G>A		non_coding_transcript_exon_variant	9/20
ABHD16A	NR_033489.2	n.674G>A		non_coding_transcript_exon_variant	7/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABHD16A	ENST00000395952.8	c.755G>A	p.Arg252Gln	missense_variant	9/20	1	NM_021160.3	ENSP00000379282	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1458986 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 725770

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Spastic paraplegia Uncertain:1

Uncertain significance, criteria provided, single submitter

research

Care4Rare-SOLVE, CHEO

Jul 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.33
CADD	Pathogenic	33
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.37	T;.
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Benign	0.025	T
MetaRNN	Pathogenic	0.82	D;D
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Uncertain	2.6	M;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.9	D;D
REVEL	Uncertain	0.44
Sift	Uncertain	0.0020	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.59
MutPred		0.80		Gain of catalytic residue at R252 (P = 0.0319);.;
MVP		0.49
MPC		1.6
ClinPred		1.0	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.38
gMVP		0.91

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

Other links and lift over

dbSNP: rs1803887518; hg19: chr6-31659444; COSMIC: COSV101013374; COSMIC: COSV101013374;