19-34328000-G-C

Variant summary

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

The NM_014686.5(GARRE1):c.953G>C(p.Ser318Thr) 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: 7.77

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.953G>C	p.Ser318Thr	missense_variant	6/14	ENST00000299505.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GARRE1	ENST00000299505.8	c.953G>C	p.Ser318Thr	missense_variant	6/14	1	NM_014686.5	P1
GARRE1	ENST00000588338.6	n.264-21120G>C		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

Nov 29, 2023

The c.953G>C (p.S318T) alteration is located in exon 6 (coding exon 5) of the KIAA0355 gene. This alteration results from a G to C substitution at nucleotide position 953, causing the serine (S) at amino acid position 318 to be replaced by a threonine (T). 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	0.14
BayesDel_addAF	Uncertain	0.070	D
BayesDel_noAF	Benign	-0.14
Cadd	Pathogenic	27
Dann	Uncertain	0.99
DEOGEN2	Benign	0.061	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0049	T
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.97	L
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.21
Sift	Benign	0.14	T
Sift4G	Uncertain	0.049	D
Polyphen		0.73	P
Vest4		0.69
MutPred		0.19		Loss of disorder (P = 0.1038);
MVP		0.20
MPC		0.76
ClinPred		0.87	D
GERP RS		5.5
Varity_R		0.25
gMVP		0.53

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: chr19-34818905;