Variant 6-37819982-A-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_021943.3(ZFAND3):c.37A>T(p.Ser13Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000187 in 1,068,004 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: not found (cov: 32)

Exomes 𝑓: 0.0000019 ( 0 hom. )

Consequence

ZFAND3
NM_021943.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.53

Variant links:

Genes affected

ZFAND3 (HGNC:18019): (zinc finger AN1-type containing 3) Predicted to enable DNA binding activity and zinc ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ZFAND3 links:

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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=0.2149325).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ZFAND3	NM_021943.3 linkuse as main transcript	c.37A>T	p.Ser13Cys	missense_variant	1/6	ENST00000287218.9
ZFAND3	NM_001410904.1 linkuse as main transcript	c.37A>T	p.Ser13Cys	missense_variant	1/5
ZFAND3	XM_011514790.3 linkuse as main transcript	c.37A>T	p.Ser13Cys	missense_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ZFAND3	ENST00000287218.9 linkuse as main transcript	c.37A>T	p.Ser13Cys	missense_variant	1/6	1	NM_021943.3	P1
ZFAND3	ENST00000373391.6 linkuse as main transcript	c.37A>T	p.Ser13Cys	missense_variant	1/5	5
ZFAND3	ENST00000474522.5 linkuse as main transcript	c.37A>T	p.Ser13Cys	missense_variant	1/6	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000187

AC:

AN:

1068004

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

505242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000255

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Dec 15, 2022

The c.37A>T (p.S13C) alteration is located in exon 1 (coding exon 1) of the ZFAND3 gene. This alteration results from a A to T substitution at nucleotide position 37, causing the serine (S) at amino acid position 13 to be replaced by a cysteine (C). 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

0.14

BayesDel_addAF

Benign

-0.099

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.063

T;.;T

Eigen

Uncertain

0.21

Eigen_PC

Benign

0.17

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.79

T;T;T

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.21

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

L;.;.

MutationTaster

Benign

0.94

D;D

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-1.8

N;N;N

REVEL

Benign

0.096

Sift

Uncertain

0.026

D;D;D

Sift4G

Uncertain

0.017

D;D;D

Polyphen

0.98

D;.;.

Vest4

0.30

MutPred

0.24

Loss of glycosylation at S13 (P = 0.0309);Loss of glycosylation at S13 (P = 0.0309);Loss of glycosylation at S13 (P = 0.0309);

MVP

0.082

MPC

0.53

ClinPred

0.90

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.25

gMVP

0.34

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