Genetic Variant ZFAND5:p.Ser139Arg (chr9-72357007-A-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001102420.3(ZFAND5):c.417T>A(p.Ser139Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000583 in 1,613,606 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: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000057 ( 0 hom. )

Consequence

ZFAND5
NM_001102420.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.77

Variant links:

Genes affected

ZFAND5 (HGNC:13008): (zinc finger AN1-type containing 5) Predicted to enable DNA binding activity and zinc ion binding activity. Predicted to act upstream of or within several processes, including face development; fibroblast migration; and platelet-derived growth factor receptor signaling pathway. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZFAND5 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=0.09002048).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFAND5	NM_001102420.3 link	c.417T>A	p.Ser139Arg	missense_variant	Exon 6 of 7	ENST00000376962.10	NP_001095890.1	O76080A0A024R219

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFAND5	ENST00000376962.10 link	c.417T>A	p.Ser139Arg	missense_variant	Exon 6 of 7	1	NM_001102420.3	ENSP00000366161.5		O76080

Frequencies

GnomAD3 genomes

AF:

0.0000724

AC:

AN:

152038

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000736

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000637

AC:

AN:

251266

Hom.:

AF XY:

0.0000884

AC XY:

AN XY:

135790

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.0000568

AC:

AN:

1461568

Hom.:

Cov.:

AF XY:

0.0000743

AC XY:

AN XY:

727086

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000255

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.0000396

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.0000724

AC:

AN:

152038

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000736

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000135

Hom.:

Bravo

AF:

0.0000907

ExAC

AF:

0.0000494

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 21, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.417T>A (p.S139R) alteration is located in exon 6 (coding exon 4) of the ZFAND5 gene. This alteration results from a T to A substitution at nucleotide position 417, causing the serine (S) at amino acid position 139 to be replaced by an arginine (R). 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

0.29

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.26

T;T;T;T;.

Eigen

Benign

-0.037

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.87

D;.;.;.;D

M_CAP

Benign

0.0034

MetaRNN

Benign

0.090

T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.55

N;N;N;N;.

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-2.0

N;N;N;N;N

REVEL

Benign

0.049

Sift

Benign

0.082

T;T;T;T;D

Sift4G

Benign

0.32

T;T;T;T;.

Polyphen

0.0040

B;B;B;B;.

Vest4

0.27

MutPred

0.14

Loss of phosphorylation at S139 (P = 0.0046);Loss of phosphorylation at S139 (P = 0.0046);Loss of phosphorylation at S139 (P = 0.0046);Loss of phosphorylation at S139 (P = 0.0046);.;

MVP

0.10

MPC

0.76

ClinPred

0.084

GERP RS

6.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.17

gMVP

0.58

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