16-377479-T-G

Variant names:

• chr16-377479-T-G
• rs11248931
• NM_021259.3:c.406A>C

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.406A>C​(p.Thr136Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,456,166 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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: -1.23
• Publications: 46 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 (MetaRNN=0.06605801).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGAP6	NM_021259.3	c.406A>C	p.Thr136Pro	missense_variant	Exon 3 of 13	ENST00000431232.7	NP_067082.2
PGAP6	XM_047434413.1	c.-174A>C		5_prime_UTR_variant	Exon 4 of 14		XP_047290369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGAP6	ENST00000431232.7	c.406A>C	p.Thr136Pro	missense_variant	Exon 3 of 13	1	NM_021259.3	ENSP00000401338.2
PGAP6	ENST00000476735.1	n.643A>C		non_coding_transcript_exon_variant	Exon 4 of 5	5
PGAP6	ENST00000250930.7	c.-174A>C		5_prime_UTR_variant	Exon 3 of 13	2		ENSP00000250930.3
PGAP6	ENST00000427313.5	c.-174A>C		5_prime_UTR_variant	Exon 3 of 5	4		ENSP00000410987.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1456166 Hom.: 0 Cov.: 68 AF XY: 0.00 AC XY: 0 AN XY: 723928

African (AFR) AF: 0.00 AC: 0 AN: 33436

American (AMR) AF: 0.00 AC: 0 AN: 44082

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26012

East Asian (EAS) AF: 0.00 AC: 0 AN: 39564

South Asian (SAS) AF: 0.00 AC: 0 AN: 85524

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51694

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109982

Other (OTH) AF: 0.00 AC: 0 AN: 60118

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 41018

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.14
DANN	Benign	0.29
DEOGEN2	Benign	0.0020	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.20	T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.55	N
PhyloP100		-1.2
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.18	N
REVEL	Benign	0.017
Sift	Benign	0.67	T
Sift4G	Benign	0.35	T
Polyphen		0.10	B
Vest4		0.067
MutPred		0.24		Loss of sheet (P = 0.0228);
MVP		0.030
MPC		0.059
ClinPred		0.025	T
GERP RS		0.98
Varity_R		0.032
gMVP		0.37

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: rs11248931; hg19: chr16-427479;