rs747922747

Variant names:

• chr16-372208-C-G
• NM_021259.3:c.2095G>C

Your query was ambiguous. Multiple possible variants found:

• chr16-372208-C-G
• chr16-372208-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021259.3(PGAP6):​c.2095G>C​(p.Val699Leu) variant causes a missense 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. 15/21 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. V699I) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PGAP6 NM_021259.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.430

Genes affected

PGAP6 (HGNC:17205): (post-GPI attachment to proteins 6) Predicted to enable phospholipase A2 activity. Located in extracellular exosome and lysosomal membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04417619).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGAP6	NM_021259.3	c.2095G>C	p.Val699Leu	missense_variant	Exon 13 of 13	ENST00000431232.7	NP_067082.2
PGAP6	XM_047434413.1	c.1516G>C	p.Val506Leu	missense_variant	Exon 14 of 14		XP_047290369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGAP6	ENST00000431232.7	c.2095G>C	p.Val699Leu	missense_variant	Exon 13 of 13	1	NM_021259.3	ENSP00000401338.2
PGAP6	ENST00000250930.7	c.1516G>C	p.Val506Leu	missense_variant	Exon 13 of 13	2		ENSP00000250930.3
PGAP6	ENST00000424078.5	c.496G>C	p.Val166Leu	missense_variant	Exon 4 of 4	3		ENSP00000397620.1
PGAP6	ENST00000448854.1	c.*334G>C		downstream_gene_variant		2		ENSP00000401931.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	9.3
DANN	Benign	0.81
DEOGEN2	Benign	0.0028	T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.61	T;T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.044	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.020	N;.
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.36	N;N
REVEL	Benign	0.045
Sift	Benign	0.49	T;T
Sift4G	Benign	0.34	T;T
Polyphen		0.036	B;.
Vest4		0.033
MutPred		0.35		Loss of helix (P = 0.1299);.;
MVP		0.076
MPC		0.047
ClinPred		0.27	T
GERP RS		-0.86
Varity_R		0.022
gMVP		0.23

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-422208;