19-34328053-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014686.5(GARRE1):c.1006C>G(p.Gln336Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GARRE1 NM_014686.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.54

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GARRE1	NM_014686.5	c.1006C>G	p.Gln336Glu	missense_variant	6/14	ENST00000299505.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GARRE1	ENST00000299505.8	c.1006C>G	p.Gln336Glu	missense_variant	6/14	1	NM_014686.5	P1
GARRE1	ENST00000588338.6	n.264-21067C>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 08, 2023

The c.1006C>G (p.Q336E) alteration is located in exon 6 (coding exon 5) of the KIAA0355 gene. This alteration results from a C to G substitution at nucleotide position 1006, causing the glutamine (Q) at amino acid position 336 to be replaced by a glutamic acid (E). 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	0.12
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
Cadd	Benign	23
Dann	Uncertain	0.99
DEOGEN2	Benign	0.043	T
Eigen	Uncertain	0.61
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.60	D
MetaSVM	Benign	-0.51	T
MutationAssessor	Benign	1.0	L
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.28
Sift	Benign	0.21	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.95	P
Vest4		0.76
MutPred		0.21		Gain of sheet (P = 0.0827);
MVP		0.29
MPC		0.71
ClinPred		0.94	D
GERP RS		5.5
Varity_R		0.26
gMVP		0.50

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-34818958;