Variant 10-45625953-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_174890.4(ZFAND4):c.1870T>G(p.Leu624Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,612,260 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

ZFAND4
NM_174890.4 missense, splice_region

Scores

Splicing: ADA: 0.00009407

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.738

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:

ZFAND4 (HGNC:):

ZFAND4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.030091405).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFAND4	NM_174890.4 linkuse as main transcript	c.1870T>G	p.Leu624Val	missense_variant, splice_region_variant	7/10	ENST00000344646.10	NP_777550.2	Q86XD8A0A024R7V9Q86WR3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZFAND4	ENST00000344646.10 linkuse as main transcript	c.1870T>G	p.Leu624Val	missense_variant, splice_region_variant	7/10	1	NM_174890.4	ENSP00000339484.5	Q86XD8
ZFAND4	ENST00000374366.7 linkuse as main transcript	c.1648T>G	p.Leu550Val	missense_variant, splice_region_variant	8/11	1		ENSP00000363486.3	J3KPC0
ZFAND4	ENST00000374371.6 linkuse as main transcript	c.570-7693T>G		intron_variant		5		ENSP00000363491.1	Q5VVY4
ZFAND4	ENST00000374370.1 linkuse as main transcript	n.1590T>G		splice_region_variant, non_coding_transcript_exon_variant	4/7	2

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000321

AC:

AN:

249112

Hom.:

AF XY:

0.0000445

AC XY:

AN XY:

134796

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000117

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000355

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000212

AC:

AN:

1459956

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

726294

show subpopulations

Gnomad4 AFR exome

AF:

0.000150

Gnomad4 AMR exome

AF:

0.000203

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:

0.00000990

Gnomad4 OTH exome

AF:

0.0000664

GnomAD4 genome

AF:

0.0000525

AC:

AN:

152304

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000756

ExAC

AF:

0.0000494

AC:

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

Nov 18, 2023

The c.1870T>G (p.L624V) alteration is located in exon 7 (coding exon 6) of the ZFAND4 gene. This alteration results from a T to G substitution at nucleotide position 1870, causing the leucine (L) at amino acid position 624 to be replaced by a valine (V). 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

0.087

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.60

CADD

Benign

7.5

DANN

Benign

0.71

DEOGEN2

Benign

0.0023

.;T

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.50

T;T

M_CAP

Benign

0.0064

MetaRNN

Benign

0.030

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

.;L

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.74

N;N

REVEL

Benign

0.044

Sift

Benign

0.14

T;T

Sift4G

Benign

0.27

T;T

Polyphen

0.0080

.;B

Vest4

0.15

MVP

0.076

MPC

0.068

ClinPred

0.089

GERP RS

0.81

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.059

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000094

dbscSNV1_RF

Benign

0.036

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