Genetic Variant CYTH3:p.Arg29Gln (chr7-6190480-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -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

Publications

0 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004227.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CYTH3	NM_004227.4	MANE Select	c.86G>A	p.Arg29Gln	missense	Exon 2 of 13	NP_004218.1	O43739-2
CYTH3	NM_001367580.1		c.-1092G>A		5_prime_UTR	Exon 2 of 13	NP_001354509.1	B7Z2V9
CYTH3	NM_001367581.1		c.-639G>A		5_prime_UTR	Exon 2 of 14	NP_001354510.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CYTH3	ENST00000350796.8	TSL:1 MANE Select	c.86G>A	p.Arg29Gln	missense	Exon 2 of 13	ENSP00000297044.7	O43739-2
CYTH3	ENST00000898314.1		c.224G>A	p.Arg75Gln	missense	Exon 3 of 14	ENSP00000568373.1
CYTH3	ENST00000898313.1		c.179G>A	p.Arg60Gln	missense	Exon 3 of 14	ENSP00000568372.1

Frequencies

GnomAD3 genomes

AF:

0.000107

AC:

AN:

112246

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.0000556

AC:

AN:

107826

AF XY:

0.0000682

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 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

African (AFR)

AF:

0.00

AC:

AN:

26228

American (AMR)

AF:

0.000193

AC:

AN:

20734

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20648

East Asian (EAS)

AF:

0.0000773

AC:

AN:

25860

South Asian (SAS)

AF:

0.0000618

AC:

AN:

64770

European-Finnish (FIN)

AF:

0.0000333

AC:

AN:

30030

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5080

European-Non Finnish (NFE)

AF:

0.000124

AC:

124

AN:

996476

Other (OTH)

AF:

0.0000600

AC:

AN:

49984

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.421

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

African (AFR)

AF:

0.000166

AC:

AN:

30106

American (AMR)

AF:

0.00

AC:

AN:

9296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3038

East Asian (EAS)

AF:

0.000566

AC:

AN:

3532

South Asian (SAS)

AF:

0.00

AC:

AN:

3426

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4332

Middle Eastern (MID)

AF:

0.00

AC:

AN:

138

European-Non Finnish (NFE)

AF:

0.0000711

AC:

AN:

56236

Other (OTH)

AF:

0.000680

AC:

AN:

1470

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000558

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000241

AC:

ExAC

AF:

0.0000319

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.38

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.32

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.94

LIST_S2

Pathogenic

0.99

M_CAP

Benign

0.031

MetaRNN

Benign

0.25

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

PhyloP100

6.2

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.96

REVEL

Benign

0.16

Sift

Benign

0.33

Sift4G

Benign

0.19

Polyphen

1.0

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

Mutation Taster

=74/26

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over