NM_013385.5:c.220A>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_013385.5(CYTH4):c.220A>G(p.Met74Val) variant causes a missense change. The variant allele was found at a frequency of 0.00371 in 1,613,002 control chromosomes in the GnomAD database, including 199 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 104 hom., cov: 33)

Exomes 𝑓: 0.0020 ( 95 hom. )

Consequence

CYTH4
NM_013385.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.99

Publications

9 publications found

Variant links:

Genes affected

CYTH4 (HGNC:9505): (cytohesin 4) This gene encodes a member of the PSCD family of proteins, which have 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 function as GEPs for ADP-ribosylation factors (ARFs), which are guanine nucleotide-binding proteins involved in vesicular trafficking pathways. This protein exhibits GEP activity in vitro with ARF1 and ARF5, but is inactive with ARF6. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2015]

CYTH4 links:

ENSG00000298470 (HGNC:):

ENSG00000298470 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004670739).

BP6

Variant 22-37296051-A-G is Benign according to our data. Variant chr22-37296051-A-G is described in ClinVar as Benign. ClinVar VariationId is 781618.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0679 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013385.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYTH4	NM_013385.5	MANE Select	c.220A>G	p.Met74Val	missense	Exon 4 of 13	NP_037517.1	Q9UIA0
	CYTH4	NM_001318024.2		c.49A>G	p.Met17Val	missense	Exon 4 of 13	NP_001304953.1	B4E2V8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CYTH4	ENST00000248901.11	TSL:1 MANE Select	c.220A>G	p.Met74Val	missense	Exon 4 of 13	ENSP00000248901.6	Q9UIA0
CYTH4	ENST00000469886.5	TSL:1	n.275A>G		non_coding_transcript_exon	Exon 4 of 5
CYTH4	ENST00000868416.1		c.217A>G	p.Met73Val	missense	Exon 4 of 13	ENSP00000538475.1

Frequencies

GnomAD3 genomes

AF:

0.0202

AC:

3067

AN:

152168

Hom.:

104

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0701

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00753

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.0162

GnomAD2 exomes

AF:

0.00501

AC:

1239

AN:

247444

AF XY:

0.00363

show subpopulations

Gnomad AFR exome

AF:

0.0700

Gnomad AMR exome

AF:

0.00323

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000985

Gnomad OTH exome

AF:

0.00215

GnomAD4 exome

AF:

0.00200

AC:

2921

AN:

1460716

Hom.:

Cov.:

AF XY:

0.00169

AC XY:

1227

AN XY:

726548

show subpopulations

African (AFR)

AF:

0.0710

AC:

2374

AN:

33446

American (AMR)

AF:

0.00399

AC:

178

AN:

44622

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26094

East Asian (EAS)

AF:

0.00

AC:

AN:

39680

South Asian (SAS)

AF:

0.000105

AC:

AN:

85982

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53358

Middle Eastern (MID)

AF:

0.000694

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.000147

AC:

163

AN:

1111436

Other (OTH)

AF:

0.00320

AC:

193

AN:

60334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

136

273

409

546

682

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

216

288

360

<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

AF:

0.0202

AC:

3071

AN:

152286

Hom.:

104

Cov.:

AF XY:

0.0194

AC XY:

1445

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.0700

AC:

2909

AN:

41552

American (AMR)

AF:

0.00752

AC:

115

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000191

AC:

AN:

68008

Other (OTH)

AF:

0.0161

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

160

320

479

639

799

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<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:

0.00719

Hom.:

Bravo

AF:

0.0222

ESP6500AA

AF:

0.0726

AC:

320

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00643

AC:

781

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.057

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

MetaRNN

Benign

0.0047

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

PhyloP100

5.0

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-4.0

REVEL

Benign

0.19

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0030

Polyphen

0.018

Vest4

0.35

MVP

0.39

MPC

0.39

ClinPred

0.040

GERP RS

5.1

Varity_R

0.50

gMVP

0.39

Mutation Taster

=90/10

polymorphism (auto)

(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