rs2071915

Variant names:

• chr16-376432-T-A
• NM_021259.3:c.928A>T

Your query was ambiguous. Multiple possible variants found:

• chr16-376432-T-A
• chr16-376432-T-C

Variant summary

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

The NM_021259.3(PGAP6):​c.928A>T​(p.Ile310Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000007 in 1,429,332 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. I310V) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: PGAP6 NM_021259.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.26

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=0.029022843).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGAP6	NM_021259.3	c.928A>T	p.Ile310Phe	missense_variant	Exon 6 of 13	ENST00000431232.7	NP_067082.2
PGAP6	XM_047434413.1	c.349A>T	p.Ile117Phe	missense_variant	Exon 7 of 14		XP_047290369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGAP6	ENST00000431232.7	c.928A>T	p.Ile310Phe	missense_variant	Exon 6 of 13	1	NM_021259.3	ENSP00000401338.2
PGAP6	ENST00000250930.7	c.349A>T	p.Ile117Phe	missense_variant	Exon 6 of 13	2		ENSP00000250930.3
PGAP6	ENST00000475348.1	n.44A>T		non_coding_transcript_exon_variant	Exon 1 of 4	2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.00e-7 AC: 1 AN: 1429332 Hom.: 0 Cov.: 71 AF XY: 0.00000141 AC XY: 1 AN XY: 706846

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.14e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.0040
DANN	Benign	0.30
DEOGEN2	Benign	0.0023	T;.
Eigen	Benign	-2.8
Eigen_PC	Benign	-2.9
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.26	T;T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.029	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-1.6	N;.
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.17	N;N
REVEL	Benign	0.010
Sift	Benign	0.10	T;T
Sift4G	Benign	0.73	T;T
Polyphen		0.0	B;.
Vest4		0.041
MutPred		0.32		Loss of catalytic residue at P312 (P = 0.0346);.;
MVP		0.014
MPC		0.057
ClinPred		0.10	T
GERP RS		-9.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.028
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr16-426432;