7-128677718-C-G

Variant names:

• chr7-128677718-C-G
• NM_001128926.4:c.493C>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001128926.4(GARIN1A):​c.493C>G​(p.Leu165Val) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: GARIN1A NM_001128926.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.718
• Publications: 0 publications found

Genes affected

GARIN1A (HGNC:27998): (golgi associated RAB2 interactor 1A)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.821

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128926.4. 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
	GARIN1A	NM_001128926.4	MANE Select	c.493C>G	p.Leu165Val	missense	Exon 3 of 5	NP_001122398.1	Q6NXP2-2
	GARIN1A	NM_001012454.6		c.520C>G	p.Leu174Val	missense	Exon 3 of 5	NP_001012457.3	Q6NXP2-1
	GARIN1A	NM_001290254.2		c.235C>G	p.Leu79Val	missense	Exon 4 of 6	NP_001277183.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GARIN1A	ENST00000682356.1	MANE Select	c.493C>G	p.Leu165Val	missense	Exon 3 of 5	ENSP00000506740.1	Q6NXP2-2
	GARIN1A	ENST00000641605.1		c.520C>G	p.Leu174Val	missense	Exon 3 of 5	ENSP00000493102.1	Q6NXP2-1
	GARIN1A	ENST00000477515.3	TSL:1	c.365+1859C>G		intron	N/A	ENSP00000419649.3	C9K0C0

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 30

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	Pathogenic	0.57
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Benign	0.70	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.039	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.72
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.34
Sift	Uncertain	0.012	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
MutPred		0.75		Gain of MoRF binding (P = 0.1666)
ClinPred		0.97	D
GERP RS		3.8
Varity_R		0.58
gMVP		0.28
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: chr7-128317772;