7-128680067-G-C

Variant names:

• chr7-128680067-G-C
• rs757554559
• NM_001128926.4:c.625G>C

Variant summary

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

The NM_001128926.4(GARIN1A):​c.625G>C​(p.Glu209Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000035 in 1,428,112 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. E209D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: GARIN1A NM_001128926.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.12
• Publications: 1 publications found

Genes affected

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

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=0.15386403).

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.625G>C	p.Glu209Gln	missense	Exon 4 of 5	NP_001122398.1	Q6NXP2-2
	GARIN1A	NM_001012454.6		c.652G>C	p.Glu218Gln	missense	Exon 4 of 5	NP_001012457.3	Q6NXP2-1
	GARIN1A	NM_001290254.2		c.367G>C	p.Glu123Gln	missense	Exon 5 of 6	NP_001277183.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GARIN1A	ENST00000682356.1	MANE Select	c.625G>C	p.Glu209Gln	missense	Exon 4 of 5	ENSP00000506740.1	Q6NXP2-2
	GARIN1A	ENST00000641605.1		c.652G>C	p.Glu218Gln	missense	Exon 4 of 5	ENSP00000493102.1	Q6NXP2-1
	GARIN1A	ENST00000477515.3	TSL:1	c.402G>C	p.Ala134Ala	synonymous	Exon 3 of 4	ENSP00000419649.3	C9K0C0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000148 AC: 3 AN: 203310 AF XY: 0.0000275

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000350 AC: 5 AN: 1428112 Hom.: 0 Cov.: 30 AF XY: 0.00000566 AC XY: 4 AN XY: 707126

African (AFR) AF: 0.00 AC: 0 AN: 32686

American (AMR) AF: 0.00 AC: 0 AN: 39758

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25496

East Asian (EAS) AF: 0.00 AC: 0 AN: 37890

South Asian (SAS) AF: 0.0000503 AC: 4 AN: 79536

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51670

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5736

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1096094

Other (OTH) AF: 0.0000169 AC: 1 AN: 59246

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000166 AC: 2

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	0.10
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.071	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		4.1
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.12
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.031	D
Polyphen		1.0	D
MutPred		0.25		Gain of glycosylation at P216 (P = 0.1314)
ClinPred		0.65	D
GERP RS		5.1
Varity_R		0.16
gMVP		0.23
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs757554559; hg19: chr7-128320121;