19-50467696-C-A

Variant names:

• chr19-50467696-C-A
• rs139575261
• NM_001308429.2:c.673G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001308429.2(GARIN5A):​c.673G>T​(p.Gly225Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,441,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 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. G225D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: GARIN5A NM_001308429.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.882
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3991865).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GARIN5A	NM_001308429.2	c.673G>T	p.Gly225Cys	missense_variant	Exon 4 of 5	ENST00000600100.6	NP_001295358.1
GARIN5A	NM_138411.3	c.625G>T	p.Gly209Cys	missense_variant	Exon 4 of 5		NP_612420.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GARIN5A	ENST00000600100.6	c.673G>T	p.Gly225Cys	missense_variant	Exon 4 of 5	1	NM_001308429.2	ENSP00000472421.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000469 AC: 1 AN: 213102 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000107

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1441190 Hom.: 0 Cov.: 31 AF XY: 0.00000140 AC XY: 1 AN XY: 715082

African (AFR) AF: 0.00 AC: 0 AN: 33136

American (AMR) AF: 0.00 AC: 0 AN: 41252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25734

East Asian (EAS) AF: 0.00 AC: 0 AN: 38662

South Asian (SAS) AF: 0.00 AC: 0 AN: 83306

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51686

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1102114

Other (OTH) AF: 0.00 AC: 0 AN: 59562

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000827 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.000063	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0038	T;.
Eigen	Benign	0.011
Eigen_PC	Benign	-0.073
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.70	T;T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.40	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L;.
PhyloP100		0.88
PrimateAI	Uncertain	0.49	T
Sift4G	Benign	0.088	T;T
Polyphen		1.0	D;D
Vest4		0.52
MutPred		0.28		Loss of MoRF binding (P = 0.1006);.;
MVP		0.20
MPC		0.74
ClinPred		0.82	D
GERP RS		1.8
Varity_R		0.19
gMVP		0.47
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs139575261; hg19: chr19-50970953;