NM_001308429.2:c.247G>A

Variant names:

• chr19-50476142-C-T
• NM_001308429.2:c.247G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001308429.2(GARIN5A):​c.247G>A​(p.Gly83Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,230 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G83A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GARIN5A NM_001308429.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0130
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08188626).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001308429.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GARIN5A	NM_001308429.2	MANE Select	c.247G>A	p.Gly83Ser	missense	Exon 1 of 5	NP_001295358.1	Q6IPT2-1
	GARIN5A	NM_138411.3		c.247G>A	p.Gly83Ser	missense	Exon 1 of 5	NP_612420.1	Q6IPT2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GARIN5A	ENST00000600100.6	TSL:1 MANE Select	c.247G>A	p.Gly83Ser	missense	Exon 1 of 5	ENSP00000472421.2	Q6IPT2-1
	GARIN5A	ENST00000595790.5	TSL:1	c.247G>A	p.Gly83Ser	missense	Exon 1 of 5	ENSP00000471272.2	Q6IPT2-2
	GARIN5A	ENST00000897783.1		c.247G>A	p.Gly83Ser	missense	Exon 1 of 5	ENSP00000567842.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461230 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726908

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52802

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111998

Other (OTH) AF: 0.00 AC: 0 AN: 60386

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.080	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L
PhyloP100		-0.013
PrimateAI	Benign	0.39	T
Sift4G	Benign	0.40	T
Polyphen		0.82	P
Vest4		0.10
MutPred		0.12		Gain of glycosylation at G83 (P = 7e-04)
MVP		0.030
MPC		0.34
ClinPred		0.60	D
GERP RS		3.3
PromoterAI		0.073	Neutral
Varity_R		0.12
gMVP		0.13
Mutation Taster		=96/4	polymorphism

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

hg19: chr19-50979399;