rs200573824

Variant names:

• chr19-42297157-C-T
• rs200573824
• NM_002573.4:c.617G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_002573.4(PAFAH1B3):​c.617G>A​(p.Arg206Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000171 in 1,613,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict 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. R206W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00017 (0 hom.)
• Consequence: PAFAH1B3 NM_002573.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.55
• Publications: 1 publications found

Genes affected

PAFAH1B3 (HGNC:8576): (platelet activating factor acetylhydrolase 1b catalytic subunit 3) This gene encodes an acetylhydrolase that catalyzes the removal of an acetyl group from the glycerol backbone of platelet-activating factor. The encoded enzyme is a subunit of the platelet-activating factor acetylhydrolase isoform 1B complex, which consists of the catalytic beta and gamma subunits and the regulatory alpha subunit. This complex functions in brain development. A translocation between this gene on chromosome 19 and the CDC-like kinase 2 gene on chromosome 1 has been observed, and was associated with cognitive disability, ataxia, and atrophy of the brain. Alternatively spliced transcript variants have been described. [provided by RefSeq, Mar 2009]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.109077305).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002573.4. 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
	PAFAH1B3	NM_002573.4	MANE Select	c.617G>A	p.Arg206Gln	missense	Exon 5 of 5	NP_002564.1	Q15102
	PAFAH1B3	NM_001145939.2		c.617G>A	p.Arg206Gln	missense	Exon 6 of 6	NP_001139411.1	A0A024R0L6
	PAFAH1B3	NM_001145940.1		c.617G>A	p.Arg206Gln	missense	Exon 6 of 6	NP_001139412.1	Q15102

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAFAH1B3	ENST00000262890.8	TSL:1 MANE Select	c.617G>A	p.Arg206Gln	missense	Exon 5 of 5	ENSP00000262890.2	Q15102
	PAFAH1B3	ENST00000538771.5	TSL:2	c.617G>A	p.Arg206Gln	missense	Exon 6 of 6	ENSP00000444935.1	Q15102
	PAFAH1B3	ENST00000877854.1		c.617G>A	p.Arg206Gln	missense	Exon 6 of 6	ENSP00000547913.1

Frequencies

GnomAD3 genomes AF: 0.000164 AC: 25 AN: 152176 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

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: 0.000309

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000119 AC: 30 AN: 251348 AF XY: 0.000103

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000255

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000172 AC: 251 AN: 1461610 Hom.: 0 Cov.: 31 AF XY: 0.000175 AC XY: 127 AN XY: 727044

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39678

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53358

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000214 AC: 238 AN: 1111828

Other (OTH) AF: 0.000166 AC: 10 AN: 60384

GnomAD4 genome AF: 0.000164 AC: 25 AN: 152176 Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 10 AN XY: 74330

African (AFR) AF: 0.0000724 AC: 3 AN: 41430

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000309 AC: 21 AN: 68034

Other (OTH) AF: 0.000478 AC: 1 AN: 2094

Alfa AF: 0.000230 Hom.: 0

Bravo AF: 0.000181

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0000824 AC: 10

EpiCase AF: 0.000327

EpiControl AF: 0.000296

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	0.086
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.48
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PhyloP100		2.6
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	0.37	N
REVEL	Benign	0.087
Sift	Benign	0.11	T
Sift4G	Benign	0.20	T
Polyphen		0.14	B
Vest4		0.16
MVP		0.50
MPC		0.45
ClinPred		0.058	T
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.069
gMVP		0.27
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: rs200573824; hg19: chr19-42801309;