rs139494055

chr3-32140328-A-Cchr3-32140328-A-G

Variant summary

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

The NM_015141.4(GPD1L):c.467A>C(p.Asn156Thr) 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. 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. N156S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GPD1L NM_015141.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.939

Genes affected

GPD1L (HGNC:28956): (glycerol-3-phosphate dehydrogenase 1 like) The protein encoded by this gene catalyzes the conversion of sn-glycerol 3-phosphate to glycerone phosphate. The encoded protein is found in the cytoplasm, associated with the plasma membrane, where it binds the sodium channel, voltage-gated, type V, alpha subunit (SCN5A). Defects in this gene are a cause of Brugada syndrome type 2 (BRS2) as well as sudden infant death syndrome (SIDS). [provided by RefSeq, Jul 2010]

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=0.2520944).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPD1L	NM_015141.4	c.467A>C	p.Asn156Thr	missense_variant	4/8	ENST00000282541.10
GPD1L	XM_006713068.3	c.326A>C	p.Asn109Thr	missense_variant	3/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPD1L	ENST00000282541.10	c.467A>C	p.Asn156Thr	missense_variant	4/8	1	NM_015141.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251334 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135834

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
Cadd	Benign	18
Dann	Benign	0.96
DEOGEN2	Benign	0.21	T;T;.;T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.68	D
LIST_S2	Uncertain	0.92	D;D;D;D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.25	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-2.9	D;D;D;D
REVEL	Benign	0.083
Sift	Benign	0.25	T;T;T;T
Sift4G	Benign	0.22	T;T;T;T
Polyphen		0.018	.;B;.;.
Vest4		0.33
MutPred		0.52		.;Gain of glycosylation at N156 (P = 0.0282);.;.;
MVP		0.66
MPC		0.45
ClinPred		0.30	T
GERP RS		-0.077
Varity_R		0.47
gMVP		0.39

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: rs139494055; hg19: chr3-32181820;