Genetic Variant ZFAND4:p.Ala677Ser (chr10-45618159-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_174890.4(ZFAND4):c.2029G>T(p.Ala677Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000911 in 1,613,102 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000085 ( 1 hom. )

Consequence

ZFAND4
NM_174890.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.44

Publications

2 publications found

Variant links:

Genes affected

ZFAND4 (HGNC:23504): (zinc finger AN1-type containing 4) Predicted to enable zinc ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ZFAND4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24527428).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174890.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZFAND4	NM_174890.4	MANE Select	c.2029G>T	p.Ala677Ser	missense	Exon 9 of 10	NP_777550.2	Q86XD8
ZFAND4	NM_001128324.2		c.2029G>T	p.Ala677Ser	missense	Exon 9 of 10	NP_001121796.1	Q86XD8
ZFAND4	NM_001282905.1		c.1807G>T	p.Ala603Ser	missense	Exon 10 of 11	NP_001269834.1	J3KPC0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZFAND4	ENST00000344646.10	TSL:1 MANE Select	c.2029G>T	p.Ala677Ser	missense	Exon 9 of 10	ENSP00000339484.5	Q86XD8
ZFAND4	ENST00000374366.7	TSL:1	c.1807G>T	p.Ala603Ser	missense	Exon 10 of 11	ENSP00000363486.3	J3KPC0
ZFAND4	ENST00000947494.1		c.2047G>T	p.Ala683Ser	missense	Exon 9 of 10	ENSP00000617553.1

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000160

AC:

AN:

250522

AF XY:

0.000170

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000925

Gnomad NFE exome

AF:

0.000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000849

AC:

124

AN:

1460816

Hom.:

Cov.:

AF XY:

0.0000881

AC XY:

AN XY:

726704

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33430

American (AMR)

AF:

0.00

AC:

AN:

44484

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26116

East Asian (EAS)

AF:

0.00

AC:

AN:

39610

South Asian (SAS)

AF:

0.00

AC:

AN:

86040

European-Finnish (FIN)

AF:

0.000899

AC:

AN:

53366

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000567

AC:

AN:

1111670

Other (OTH)

AF:

0.000166

AC:

AN:

60334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

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

AF:

0.000151

AC:

AN:

152286

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41560

American (AMR)

AF:

0.00

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00104

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

68022

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

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:

0.0000608

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.000123

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

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

0.14

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.014

Eigen

Pathogenic

0.70

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.85

M_CAP

Uncertain

0.086

MetaRNN

Benign

0.25

MetaSVM

Benign

-0.65

MutationAssessor

Benign

1.4

PhyloP100

5.4

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-1.6

REVEL

Benign

0.083

Sift

Benign

0.11

Sift4G

Benign

0.093

Polyphen

0.13

Vest4

0.45

MutPred

0.67

Gain of sheet (P = 0.0125)

MVP

0.60

MPC

0.17

ClinPred

0.18

GERP RS

6.0

Varity_R

0.21

gMVP

0.45

Mutation Taster

=44/56

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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