Variant chr7-128677605-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001128926.4(GARIN1A):c.380G>A(p.Arg127Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000968 in 1,612,860 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00073 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00099 ( 1 hom. )

Consequence

GARIN1A
NM_001128926.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0910

Variant links:

Genes affected

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

GARIN1A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.010729164).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GARIN1A	NM_001128926.4 linkuse as main transcript	c.380G>A	p.Arg127Gln	missense_variant	3/5	ENST00000682356.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GARIN1A	ENST00000682356.1 linkuse as main transcript	c.380G>A	p.Arg127Gln	missense_variant	3/5		NM_001128926.4	P4	Q6NXP2-2

Frequencies

GnomAD3 genomes

AF:

0.000732

AC:

111

AN:

151730

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000291

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000460

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00124

Gnomad OTH

AF:

0.000962

GnomAD3 exomes

AF:

0.000600

AC:

149

AN:

248338

Hom.:

AF XY:

0.000542

AC XY:

AN XY:

134752

show subpopulations

Gnomad AFR exome

AF:

0.000261

Gnomad AMR exome

AF:

0.000407

Gnomad ASJ exome

AF:

0.00150

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000656

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000960

Gnomad OTH exome

AF:

0.000993

GnomAD4 exome

AF:

0.000993

AC:

1451

AN:

1461036

Hom.:

Cov.:

AF XY:

0.000974

AC XY:

708

AN XY:

726756

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.000425

Gnomad4 ASJ exome

AF:

0.00111

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00120

Gnomad4 OTH exome

AF:

0.000862

GnomAD4 genome

AF:

0.000731

AC:

111

AN:

151824

Hom.:

Cov.:

AF XY:

0.000661

AC XY:

AN XY:

74180

show subpopulations

Gnomad4 AFR

AF:

0.000290

Gnomad4 AMR

AF:

0.000460

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00124

Gnomad4 OTH

AF:

0.000952

Alfa

AF:

0.00110

Hom.:

Bravo

AF:

0.000744

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00193

AC:

ExAC

AF:

0.000554

AC:

EpiCase

AF:

0.000982

EpiControl

AF:

0.00119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 22, 2021

The c.407G>A (p.R136Q) alteration is located in exon 3 (coding exon 3) of the FAM71F2 gene. This alteration results from a G to A substitution at nucleotide position 407, causing the arginine (R) at amino acid position 136 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0064

T;.

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.60

T;T

M_CAP

Benign

0.0064

MetaRNN

Benign

0.011

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;.

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.30

Polyphen

0.20

B;B

ClinPred

0.017

GERP RS

1.3

Varity_R

0.093

gMVP

0.19

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over