Variant 7-6165552-C-T 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_004227.4(CYTH3):c.965G>A(p.Arg322Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,630 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: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

CYTH3
NM_004227.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.97

Variant links:

Genes affected

CYTH3 (HGNC:9504): (cytohesin 3) This gene encodes a member of the PSCD (pleckstrin homology, Sec7 and coiled-coil domains) family. PSCD family members have identical structural organization that consists of an N-terminal coiled-coil motif, a central Sec7 domain, and a C-terminal pleckstrin homology (PH) domain. The coiled-coil motif is involved in homodimerization, the Sec7 domain contains guanine-nucleotide exchange protein (GEP) activity, and the PH domain interacts with phospholipids and is responsible for association of PSCDs with membranes. Members of this family appear to mediate the regulation of protein sorting and membrane trafficking. This encoded protein is involved in the control of Golgi structure and function, and it may have a physiological role in regulating ADP-ribosylation factor protein 6 (ARF) functions, in addition to acting on ARF1. [provided by RefSeq, Jul 2008]

CYTH3 links:

CYTH3 (HGNC:):

CYTH3 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=0.23313472).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYTH3	NM_004227.4 linkuse as main transcript	c.965G>A	p.Arg322Gln	missense_variant	11/13	ENST00000350796.8	NP_004218.1	O43739-2
CYTH3	NM_001367580.1 linkuse as main transcript	c.710G>A	p.Arg237Gln	missense_variant	11/13		NP_001354509.1
CYTH3	NM_001367581.1 linkuse as main transcript	c.464G>A	p.Arg155Gln	missense_variant	12/14		NP_001354510.1
CYTH3	NM_001367582.1 linkuse as main transcript	c.464G>A	p.Arg155Gln	missense_variant	6/8		NP_001354511.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CYTH3	ENST00000350796.8 linkuse as main transcript	c.965G>A	p.Arg322Gln	missense_variant	11/13	1	NM_004227.4	ENSP00000297044.7	O43739-2
CYTH3	ENST00000495176.5 linkuse as main transcript	n.567G>A		non_coding_transcript_exon_variant	3/3	4
CYTH3	ENST00000465320.1 linkuse as main transcript	n.145-125G>A		intron_variant		4
CYTH3	ENST00000461891.5 linkuse as main transcript	n.*15G>A		downstream_gene_variant		4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461630

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727114

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Jan 02, 2024

The c.965G>A (p.R322Q) alteration is located in exon 11 (coding exon 11) of the CYTH3 gene. This alteration results from a G to A substitution at nucleotide position 965, causing the arginine (R) at amino acid position 322 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

Uncertain

0.38

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.40

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.49

.;T

Eigen

Benign

-0.11

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.89

D;D

M_CAP

Benign

0.017

MetaRNN

Benign

0.23

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.70

.;N

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-1.1

N;.

REVEL

Benign

0.093

Sift

Benign

0.23

T;.

Sift4G

Benign

0.22

T;T

Polyphen

0.16

B;.

Vest4

0.47

MVP

0.34

MPC

1.6

ClinPred

0.87

GERP RS

5.4

Varity_R

0.46

gMVP

0.65

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