16-372187-T-A

Position:

• chr16-372187-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021259.3(PGAP6):​c.2116A>T​(p.Ile706Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PGAP6 NM_021259.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.744

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09406948).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGAP6	NM_021259.3	c.2116A>T	p.Ile706Phe	missense_variant	13/13	ENST00000431232.7	NP_067082.2
PGAP6	XM_047434413.1	c.1537A>T	p.Ile513Phe	missense_variant	14/14		XP_047290369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PGAP6	ENST00000431232.7	c.2116A>T	p.Ile706Phe	missense_variant	13/13	1	NM_021259.3	ENSP00000401338.2
PGAP6	ENST00000250930.7	c.1537A>T	p.Ile513Phe	missense_variant	13/13	2		ENSP00000250930.3
PGAP6	ENST00000424078.5	c.517A>T	p.Ile173Phe	missense_variant	4/4	3		ENSP00000397620.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 11, 2021

The c.2116A>T (p.I706F) alteration is located in exon 13 (coding exon 13) of the TMEM8A gene. This alteration results from a A to T substitution at nucleotide position 2116, causing the isoleucine (I) at amino acid position 706 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	8.0
DANN	Benign	0.87
DEOGEN2	Benign	0.068	T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.71	T;T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.094	T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.8	L;.
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-2.8	D;D
REVEL	Benign	0.20
Sift	Uncertain	0.0090	D;D
Sift4G	Uncertain	0.0080	D;D
Polyphen		0.97	D;.
Vest4		0.20
MutPred		0.31		Gain of catalytic residue at I706 (P = 0.0203);.;
MVP		0.081
MPC		0.24
ClinPred		0.50	T
GERP RS		-8.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.65

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-422187;