rs11248931

Positions:

• chr16-377479-T-C
• chr16-377479-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021259.3(PGAP6):​c.406A>G​(p.Thr136Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 1,607,742 control chromosomes in the GnomAD database, including 266,285 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.57 (25186 hom., cov: 33)
  • Exomes 𝑓: 0.57 (241099 hom.)
• Consequence: PGAP6 NM_021259.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.234334E-5).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGAP6	NM_021259.3	c.406A>G	p.Thr136Ala	missense_variant	3/13	ENST00000431232.7	NP_067082.2
PGAP6	XM_047434413.1	c.-174A>G		5_prime_UTR_variant	4/14		XP_047290369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PGAP6	ENST00000431232.7	c.406A>G	p.Thr136Ala	missense_variant	3/13	1	NM_021259.3	ENSP00000401338	P2
PGAP6	ENST00000250930.7	c.-174A>G		5_prime_UTR_variant	3/13	2		ENSP00000250930	A2
PGAP6	ENST00000427313.5	c.-174A>G		5_prime_UTR_variant	3/5	4		ENSP00000410987
PGAP6	ENST00000476735.1	n.643A>G		non_coding_transcript_exon_variant	4/5	5

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86635 AN: 151786 Hom.: 25157 Cov.: 33

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.578

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.438

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.702

Gnomad FIN AF: 0.567

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.521

GnomAD3 exomes AF: 0.538 AC: 128380 AN: 238422 Hom.: 35953 AF XY: 0.553 AC XY: 71849 AN XY: 129820

Gnomad AFR exome AF: 0.629

Gnomad AMR exome AF: 0.415

Gnomad ASJ exome AF: 0.438

Gnomad EAS exome AF: 0.309

Gnomad SAS exome AF: 0.709

Gnomad FIN exome AF: 0.555

Gnomad NFE exome AF: 0.562

Gnomad OTH exome AF: 0.536

GnomAD4 exome AF: 0.571 AC: 831857 AN: 1455840 Hom.: 241099 Cov.: 68 AF XY: 0.575 AC XY: 416365 AN XY: 723736

Gnomad4 AFR exome AF: 0.642

Gnomad4 AMR exome AF: 0.425

Gnomad4 ASJ exome AF: 0.440

Gnomad4 EAS exome AF: 0.306

Gnomad4 SAS exome AF: 0.707

Gnomad4 FIN exome AF: 0.558

Gnomad4 NFE exome AF: 0.579

Gnomad4 OTH exome AF: 0.557

GnomAD4 genome AF: 0.571 AC: 86727 AN: 151902 Hom.: 25186 Cov.: 33 AF XY: 0.571 AC XY: 42376 AN XY: 74254

Gnomad4 AFR AF: 0.637

Gnomad4 AMR AF: 0.488

Gnomad4 ASJ AF: 0.438

Gnomad4 EAS AF: 0.312

Gnomad4 SAS AF: 0.704

Gnomad4 FIN AF: 0.567

Gnomad4 NFE AF: 0.569

Gnomad4 OTH AF: 0.522

Alfa AF: 0.551 Hom.: 28530

Bravo AF: 0.557

TwinsUK AF: 0.593 AC: 2199

ALSPAC AF: 0.581 AC: 2240

ESP6500AA AF: 0.623 AC: 2729

ESP6500EA AF: 0.567 AC: 4876

ExAC AF: 0.538 AC: 64606

Asia WGS AF: 0.539 AC: 1873 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.84	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.018
DANN	Benign	0.21
DEOGEN2	Benign	0.0033	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.18	T
MetaRNN	Benign	0.000012	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.34	N
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.16	N
REVEL	Benign	0.019
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.0080
MPC		0.041
ClinPred		0.0017	T
GERP RS		0.98
Varity_R		0.013
gMVP		0.26

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

LitVar

Other links and lift over

dbSNP: rs11248931; hg19: chr16-427479; COSMIC: COSV51737664; COSMIC: COSV51737664;