16-372624-A-G

Variant names:

• chr16-372624-A-G
• rs761820371
• NM_021259.3:c.2006T>C

Variant summary

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

The NM_021259.3(PGAP6):​c.2006T>C​(p.Met669Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,404 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. M669K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PGAP6 NM_021259.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.33
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021259.3. 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
	PGAP6	NM_021259.3	MANE Select	c.2006T>C	p.Met669Thr	missense	Exon 12 of 13	NP_067082.2	Q9HCN3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGAP6	ENST00000431232.7	TSL:1 MANE Select	c.2006T>C	p.Met669Thr	missense	Exon 12 of 13	ENSP00000401338.2	Q9HCN3
	PGAP6	ENST00000946607.1		c.2195T>C	p.Met732Thr	missense	Exon 12 of 13	ENSP00000616666.1
	PGAP6	ENST00000930879.1		c.2027T>C	p.Met676Thr	missense	Exon 12 of 13	ENSP00000600938.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459404 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726020

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51582

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111478

Other (OTH) AF: 0.00 AC: 0 AN: 60340

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Uncertain	0.087	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T
Eigen	Pathogenic	0.69
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.66	T
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-0.58	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		7.3
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-3.6	D
REVEL	Uncertain	0.37
Sift	Uncertain	0.020	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.82
MutPred		0.43		Loss of helix (P = 0.079)
MVP		0.56
MPC		0.31
ClinPred		0.99	D
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.32
gMVP		0.67

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: rs761820371; hg19: chr16-422624;