chr19-50467792-C-G

Variant names:

• chr19-50467792-C-G
• rs768507803
• NM_001308429.2:c.577G>C

Variant summary

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

The NM_001308429.2(GARIN5A):​c.577G>C​(p.Asp193His) 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. 11/19 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. D193N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: GARIN5A NM_001308429.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51
• 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=0.35934958).

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.577G>C	p.Asp193His	missense	Exon 4 of 5	NP_001295358.1	Q6IPT2-1
	GARIN5A	NM_138411.3		c.529G>C	p.Asp177His	missense	Exon 4 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.577G>C	p.Asp193His	missense	Exon 4 of 5	ENSP00000472421.2	Q6IPT2-1
	GARIN5A	ENST00000595790.5	TSL:1	c.529G>C	p.Asp177His	missense	Exon 4 of 5	ENSP00000471272.2	Q6IPT2-2
	GARIN5A	ENST00000897783.1		c.601G>C	p.Asp201His	missense	Exon 4 of 5	ENSP00000567842.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.056	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		-1.5
PrimateAI	Benign	0.38	T
Sift4G	Uncertain	0.012	D
Polyphen		1.0	D
Vest4		0.48
MutPred		0.53		Loss of catalytic residue at D193 (P = 0.0251)
MVP		0.15
MPC		0.76
ClinPred		0.78	D
GERP RS		-2.6
Varity_R		0.31
gMVP		0.58
Mutation Taster		=97/3	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

dbSNP: rs768507803; hg19: chr19-50971049;