chr16-374420-C-A

Variant names:

• chr16-374420-C-A
• rs3743888
• NM_021259.3:c.1577-21G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021259.3(PGAP6):​c.1577-21G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000194 in 1,544,374 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PGAP6 NM_021259.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.536
• Publications: 17 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGAP6	NM_021259.3	c.1577-21G>T		intron_variant	Intron 9 of 12	ENST00000431232.7	NP_067082.2
PGAP6	XM_047434413.1	c.998-21G>T		intron_variant	Intron 10 of 13		XP_047290369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGAP6	ENST00000431232.7	c.1577-21G>T		intron_variant	Intron 9 of 12	1	NM_021259.3	ENSP00000401338.2

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151864 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000508 AC: 1 AN: 196782 AF XY: 0.00000933

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000144 AC: 2 AN: 1392510 Hom.: 0 Cov.: 40 AF XY: 0.00000146 AC XY: 1 AN XY: 686734

African (AFR) AF: 0.00 AC: 0 AN: 32064

American (AMR) AF: 0.00 AC: 0 AN: 38718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22916

East Asian (EAS) AF: 0.00 AC: 0 AN: 38984

South Asian (SAS) AF: 0.0000127 AC: 1 AN: 78988

European-Finnish (FIN) AF: 0.0000268 AC: 1 AN: 37254

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3962

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1081950

Other (OTH) AF: 0.00 AC: 0 AN: 57674

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151864 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74126

African (AFR) AF: 0.00 AC: 0 AN: 41344

American (AMR) AF: 0.00 AC: 0 AN: 15262

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

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10550

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67942

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.00 Hom.: 2331

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.34
DANN	Benign	0.20
PhyloP100		-0.54
PromoterAI		0.0067	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3743888; hg19: chr16-424420;