Variant 7-6190480-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_004227.4(CYTH3):c.86G>A(p.Arg29Gln) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 28)

Exomes 𝑓: 0.00011 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CYTH3
NM_004227.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.17

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 Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.24633947).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYTH3	NM_004227.4 linkuse as main transcript	c.86G>A	p.Arg29Gln	missense_variant	2/13	ENST00000350796.8	NP_004218.1	O43739-2
CYTH3	NM_001367580.1 linkuse as main transcript	c.-1092G>A		5_prime_UTR_variant	2/13		NP_001354509.1
CYTH3	NM_001367581.1 linkuse as main transcript	c.-639G>A		5_prime_UTR_variant	2/14		NP_001354510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYTH3	ENST00000350796.8 linkuse as main transcript	c.86G>A	p.Arg29Gln	missense_variant	2/13	1	NM_004227.4	ENSP00000297044.7		O43739-2
CYTH3	ENST00000482460.1 linkuse as main transcript	n.223G>A		non_coding_transcript_exon_variant	2/5	3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

112246

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000166

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000565

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000711

Gnomad OTH

AF:

0.000685

GnomAD3 exomes

AF:

0.0000556

AC:

AN:

107826

Hom.:

AF XY:

0.0000682

AC XY:

AN XY:

58638

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000154

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000155

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000634

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000111

AC:

138

AN:

1239810

Hom.:

Cov.:

AF XY:

0.000117

AC XY:

AN XY:

609384

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000193

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000773

Gnomad4 SAS exome

AF:

0.0000618

Gnomad4 FIN exome

AF:

0.0000333

Gnomad4 NFE exome

AF:

0.000124

Gnomad4 OTH exome

AF:

0.0000600

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000107

AC:

AN:

112278

Hom.:

Cov.:

AF XY:

0.000133

AC XY:

AN XY:

52460

show subpopulations

Gnomad4 AFR

AF:

0.000166

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000566

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000711

Gnomad4 OTH

AF:

0.000680

Alfa

AF:

0.0000558

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000241

AC:

ExAC

AF:

0.0000319

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

Jan 02, 2024

The c.86G>A (p.R29Q) alteration is located in exon 2 (coding exon 2) of the CYTH3 gene. This alteration results from a G to A substitution at nucleotide position 86, causing the arginine (R) at amino acid position 29 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

0.11

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.38

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.32

.;T

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.94

LIST_S2

Pathogenic

0.99

D;D

M_CAP

Benign

0.031

MetaRNN

Benign

0.25

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;L

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.96

N;.

REVEL

Benign

0.16

Sift

Benign

0.33

T;.

Sift4G

Benign

0.19

T;T

Polyphen

1.0

D;.

Vest4

0.39

MVP

0.52

MPC

0.065

ClinPred

0.24

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.49

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

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