chr7-128680067-G-T

Variant names:

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

Variant summary

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

The NM_001128926.4(GARIN1A):​c.625G>T​(p.Glu209*) variant causes a stop gained change. The variant allele was found at a frequency of 0.0000014 in 1,428,112 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: GARIN1A NM_001128926.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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>T	p.Glu209*	stop_gained	Exon 4 of 5	NP_001122398.1	Q6NXP2-2
	GARIN1A	NM_001012454.6		c.652G>T	p.Glu218*	stop_gained	Exon 4 of 5	NP_001012457.3	Q6NXP2-1
	GARIN1A	NM_001290254.2		c.367G>T	p.Glu123*	stop_gained	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>T	p.Glu209*	stop_gained	Exon 4 of 5	ENSP00000506740.1	Q6NXP2-2
	GARIN1A	ENST00000641605.1		c.652G>T	p.Glu218*	stop_gained	Exon 4 of 5	ENSP00000493102.1	Q6NXP2-1
	GARIN1A	ENST00000477515.3	TSL:1	c.402G>T	p.Ala134Ala	synonymous	Exon 3 of 4	ENSP00000419649.3	C9K0C0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1428112 Hom.: 0 Cov.: 30 AF XY: 0.00000141 AC XY: 1 AN XY: 707126

⚠️ 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: 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: 0.00 AC: 0 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: 0.00000182 AC: 2 AN: 1096094

Other (OTH) AF: 0.00 AC: 0 AN: 59246

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000000000983081), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	36
DANN	Uncertain	1.0
Eigen	Pathogenic	0.73
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Benign	0.71	D
PhyloP100		4.1
GERP RS		5.1
Mutation Taster		=122/78	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.29		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.29		Position offset: -36

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs757554559; hg19: chr7-128320121;