19-50476141-C-A

Variant names:

• chr19-50476141-C-A
• rs559536050
• NM_001308429.2:c.248G>T

Variant summary

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

The NM_001308429.2(GARIN5A):​c.248G>T​(p.Gly83Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 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: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: GARIN5A NM_001308429.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.741

Genes affected

GARIN5A (HGNC:25107): (golgi associated RAB2 interactor 5A)

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=0.13425866).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GARIN5A	NM_001308429.2	c.248G>T	p.Gly83Val	missense_variant	Exon 1 of 5	ENST00000600100.6	NP_001295358.1
GARIN5A	NM_138411.3	c.248G>T	p.Gly83Val	missense_variant	Exon 1 of 5		NP_612420.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GARIN5A	ENST00000600100.6	c.248G>T	p.Gly83Val	missense_variant	Exon 1 of 5	1	NM_001308429.2	ENSP00000472421.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461210 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 726902

Gnomad4 AFR exome AF: 0.0000597

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.080	T;.
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.097	N
LIST_S2	Benign	0.56	T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L;L
PrimateAI	Benign	0.40	T
Sift4G	Benign	0.15	T;T
Polyphen		0.99	D;D
Vest4		0.28
MutPred		0.10		Loss of catalytic residue at G84 (P = 0.098);Loss of catalytic residue at G84 (P = 0.098);
MVP		0.13
MPC		0.77
ClinPred		0.88	D
GERP RS		3.2
Varity_R		0.14
gMVP		0.13

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: rs559536050; hg19: chr19-50979398;