Genetic Variant GARIN5A:p.Thr245Met (chr19-50467635-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001308429.2(GARIN5A):c.734C>T(p.Thr245Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000447 in 1,565,532 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 (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000047 ( 0 hom. )

Consequence

GARIN5A
NM_001308429.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.27

Publications

0 publications found

Variant links:

Genes affected

GARIN5A (HGNC:25107): (golgi associated RAB2 interactor 5A)

GARIN5A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.17105275).

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.734C>T	p.Thr245Met	missense	Exon 4 of 5	NP_001295358.1	Q6IPT2-1
	GARIN5A	NM_138411.3		c.686C>T	p.Thr229Met	missense	Exon 4 of 5	NP_612420.1	Q6IPT2-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GARIN5A	ENST00000600100.6	TSL:1 MANE Select	c.734C>T	p.Thr245Met	missense	Exon 4 of 5	ENSP00000472421.2	Q6IPT2-1
GARIN5A	ENST00000595790.5	TSL:1	c.686C>T	p.Thr229Met	missense	Exon 4 of 5	ENSP00000471272.2	Q6IPT2-2
GARIN5A	ENST00000897783.1		c.758C>T	p.Thr253Met	missense	Exon 4 of 5	ENSP00000567842.1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

151980

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000387

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000227

AC:

AN:

175900

AF XY:

0.0000107

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000760

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000414

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000467

AC:

AN:

1413434

Hom.:

Cov.:

AF XY:

0.0000515

AC XY:

AN XY:

698530

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32292

American (AMR)

AF:

0.00

AC:

AN:

37000

Ashkenazi Jewish (ASJ)

AF:

0.0000395

AC:

AN:

25298

East Asian (EAS)

AF:

0.00

AC:

AN:

37012

South Asian (SAS)

AF:

0.0000124

AC:

AN:

80374

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50166

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5714

European-Non Finnish (NFE)

AF:

0.0000580

AC:

AN:

1086942

Other (OTH)

AF:

0.0000171

AC:

AN:

58636

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

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

AF:

0.0000263

AC:

AN:

152098

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41488

American (AMR)

AF:

0.00

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000387

AC:

AN:

5162

South Asian (SAS)

AF:

0.00

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

67982

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000565

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000336

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.030

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.025

Eigen

Uncertain

0.24

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.64

M_CAP

Benign

0.063

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

PhyloP100

2.3

PrimateAI

Uncertain

0.60

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.42

MutPred

0.091

Loss of glycosylation at T245 (P = 0.0961)

MVP

0.15

MPC

0.73

ClinPred

0.81

GERP RS

3.6

Varity_R

0.10

gMVP

0.52

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over