rs117908591

Positions:

chr8-105802369-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_012082.4(ZFPM2):c.2287G>A(p.Val763Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00416 in 1,613,702 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0032 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0043 ( 17 hom. )

Consequence

ZFPM2
NM_012082.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 4.16

Variant links:

Genes affected

ZFPM2 (HGNC:16700): (zinc finger protein, FOG family member 2) The zinc finger protein encoded by this gene is a widely expressed member of the FOG family of transcription factors. The family members modulate the activity of GATA family proteins, which are important regulators of hematopoiesis and cardiogenesis in mammals. It has been demonstrated that the protein can both activate and down-regulate expression of GATA-target genes, suggesting different modulation in different promoter contexts. A related mRNA suggests an alternatively spliced product but this information is not yet fully supported by the sequence. [provided by RefSeq, Jul 2008]

ZFPM2 links:

ZFPM2-AS1 (HGNC:50698): (ZFPM2 antisense RNA 1)

ZFPM2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004432678).

BP6

Variant 8-105802369-G-A is Benign according to our data. Variant chr8-105802369-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 414003.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-105802369-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00322 (490/152238) while in subpopulation NFE AF= 0.00497 (338/68020). AF 95% confidence interval is 0.00453. There are 1 homozygotes in gnomad4. There are 235 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 490 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFPM2	NM_012082.4 linkuse as main transcript	c.2287G>A	p.Val763Ile	missense_variant	8/8	ENST00000407775.7	NP_036214.2
ZFPM2-AS1	NR_125797.1 linkuse as main transcript	n.191-3927C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFPM2	ENST00000407775.7 linkuse as main transcript	c.2287G>A	p.Val763Ile	missense_variant	8/8	1	NM_012082.4	ENSP00000384179	P1	Q8WW38-1
ZFPM2-AS1	ENST00000520433.5 linkuse as main transcript	n.212-3927C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00322

AC:

490

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00459

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00396

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00497

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.00266

AC:

656

AN:

247080

Hom.:

AF XY:

0.00271

AC XY:

364

AN XY:

134132

show subpopulations

Gnomad AFR exome

AF:

0.000653

Gnomad AMR exome

AF:

0.00142

Gnomad ASJ exome

AF:

0.00210

Gnomad EAS exome

AF:

0.000112

Gnomad SAS exome

AF:

0.00111

Gnomad FIN exome

AF:

0.00269

Gnomad NFE exome

AF:

0.00418

Gnomad OTH exome

AF:

0.00283

GnomAD4 exome

AF:

0.00426

AC:

6230

AN:

1461464

Hom.:

Cov.:

AF XY:

0.00420

AC XY:

3052

AN XY:

727012

show subpopulations

Gnomad4 AFR exome

AF:

0.000627

Gnomad4 AMR exome

AF:

0.00157

Gnomad4 ASJ exome

AF:

0.00199

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00112

Gnomad4 FIN exome

AF:

0.00240

Gnomad4 NFE exome

AF:

0.00511

Gnomad4 OTH exome

AF:

0.00295

GnomAD4 genome

AF:

0.00322

AC:

490

AN:

152238

Hom.:

Cov.:

AF XY:

0.00316

AC XY:

235

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.000722

Gnomad4 AMR

AF:

0.00458

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00396

Gnomad4 NFE

AF:

0.00497

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.00427

Hom.:

Bravo

AF:

0.00305

TwinsUK

AF:

0.00378

AC:

ALSPAC

AF:

0.00675

AC:

ESP6500AA

AF:

0.000750

AC:

ESP6500EA

AF:

0.00444

AC:

ExAC

AF:

0.00243

AC:

294

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00496

EpiControl

AF:

0.00439

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2023	ZFPM2: BP4, BS2 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Aug 08, 2017	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

46,XY sex reversal 9

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 21, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.27

T;T;T

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.19

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.82

T;.;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.0044

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

L;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.16

N;N;N

REVEL

Benign

0.095

Sift

Benign

0.14

T;T;T

Sift4G

Benign

0.27

T;T;T

Polyphen

0.58

P;.;.

Vest4

0.10

MVP

0.14

MPC

0.12

ClinPred

0.010

GERP RS

4.7

Varity_R

0.031

gMVP

0.16

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