Genetic Variant GARIN1B:p.Glu242Gln (chr7-128723233-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001282788.3(GARIN1B):c.724G>C(p.Glu242Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,374 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

GARIN1B
NM_001282788.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.07

Publications

0 publications found

Variant links:

Genes affected

GARIN1B (HGNC:30704): (golgi associated RAB2 interactor 1B)

GARIN1B links:

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ACMG classification

Classification was made for transcript

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=0.34364283).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282788.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GARIN1B	NM_001282788.3	MANE Select	c.724G>C	p.Glu242Gln	missense	Exon 4 of 7	NP_001269717.1	Q96KD3-2
GARIN1B	NM_032599.4		c.724G>C	p.Glu242Gln	missense	Exon 4 of 7	NP_115988.1	Q96KD3-1
GARIN1B	NM_001282789.2		c.427G>C	p.Glu143Gln	missense	Exon 5 of 8	NP_001269718.1	Q96KD3-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GARIN1B	ENST00000621392.5	TSL:5 MANE Select	c.724G>C	p.Glu242Gln	missense	Exon 4 of 7	ENSP00000477573.2	Q96KD3-2
GARIN1B	ENST00000315184.9	TSL:1	c.724G>C	p.Glu242Gln	missense	Exon 4 of 7	ENSP00000326652.4	Q96KD3-1
GARIN1B	ENST00000471558.5	TSL:1	n.724G>C		non_coding_transcript_exon	Exon 4 of 6	ENSP00000418672.1	F8WC62

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460374

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726512

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

33442

American (AMR)

AF:

0.00

AC:

AN:

44678

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26092

East Asian (EAS)

AF:

0.00

AC:

AN:

39652

South Asian (SAS)

AF:

0.00

AC:

AN:

86210

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53286

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1110970

Other (OTH)

AF:

0.0000166

AC:

AN:

60296

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000203476), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.067

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.80

M_CAP

Benign

0.0095

MetaRNN

Benign

0.34

MetaSVM

Benign

-0.74

MutationAssessor

Benign

1.6

PhyloP100

4.1

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.094

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.014

Polyphen

0.92

Vest4

0.21

MutPred

0.11

Gain of glycosylation at P240 (P = 0.0798)

MVP

0.34

MPC

0.73

ClinPred

0.96

GERP RS

5.2

Varity_R

0.11

gMVP

0.33

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.20

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.20

Position offset: -36

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over