Variant 19-34300916-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014686.5(GARRE1):c.443C>G(p.Ala148Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000249 in 1,606,856 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000025 ( 1 hom. )

Consequence

GARRE1
NM_014686.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.78

Variant links:

Genes affected

GARRE1 (HGNC:29016): (granule associated Rac and RHOG effector 1) Enables CCR4-NOT complex binding activity and small GTPase binding activity. Involved in Rac protein signal transduction. Located in P-body. [provided by Alliance of Genome Resources, Apr 2022]

GARRE1 links:

GARRE1 (HGNC:):

GARRE1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06803891).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GARRE1	NM_014686.5 linkuse as main transcript	c.443C>G	p.Ala148Gly	missense_variant	2/14	ENST00000299505.8	NP_055501.2	O15063

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GARRE1	ENST00000299505.8 linkuse as main transcript	c.443C>G	p.Ala148Gly	missense_variant	2/14	1	NM_014686.5	ENSP00000299505.4	O15063
GARRE1	ENST00000588470.5 linkuse as main transcript	c.71C>G	p.Ala24Gly	missense_variant	3/4	5		ENSP00000475249.1	U3KPV0
GARRE1	ENST00000588338.6 linkuse as main transcript	n.263+993C>G		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000135

AC:

AN:

245010

Hom.:

AF XY:

0.0000676

AC XY:

AN XY:

133060

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000955

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.0000254

AC:

AN:

1454624

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

723904

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000827

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152232

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000491

ExAC

AF:

0.000115

AC:

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

Jul 09, 2024

The c.443C>G (p.A148G) alteration is located in exon 2 (coding exon 1) of the KIAA0355 gene. This alteration results from a C to G substitution at nucleotide position 443, causing the alanine (A) at amino acid position 148 to be replaced by a glycine (G). 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

0.23

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.073

T;.

Eigen

Uncertain

0.19

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.93

D;D

M_CAP

Benign

0.018

MetaRNN

Benign

0.068

T;T

MetaSVM

Benign

-0.81

MutationAssessor

Benign

0.69

N;.

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-1.6

N;.

REVEL

Benign

0.14

Sift

Benign

0.059

T;.

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.36

B;.

Vest4

0.33

MutPred

0.26

Gain of relative solvent accessibility (P = 0.0023);.;

MVP

0.068

MPC

0.26

ClinPred

0.092

GERP RS

5.3

Varity_R

0.24

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