NM_012082.4:c.3164C>T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_012082.4(ZFPM2):c.3164C>T(p.Ala1055Val) variant causes a missense change. The variant allele was found at a frequency of 0.0107 in 1,604,796 control chromosomes in the GnomAD database, including 1,516 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.057 ( 796 hom., cov: 32)

Exomes 𝑓: 0.0059 ( 720 hom. )

Consequence

ZFPM2
NM_012082.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 6.08

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=0.0015640557).

BP6

Variant 8-105803246-C-T is Benign according to our data. Variant chr8-105803246-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 414008.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFPM2	NM_012082.4 link	c.3164C>T	p.Ala1055Val	missense_variant	Exon 8 of 8	ENST00000407775.7	NP_036214.2	Q8WW38-1Q9NPQ0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFPM2	ENST00000407775.7 link	c.3164C>T	p.Ala1055Val	missense_variant	Exon 8 of 8	1	NM_012082.4	ENSP00000384179.2		Q8WW38-1

Frequencies

GnomAD3 genomes

AF:

0.0569

AC:

8652

AN:

152076

Hom.:

792

Cov.:

show subpopulations

Gnomad AFR

AF:

0.196

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0263

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000691

Gnomad OTH

AF:

0.0354

GnomAD3 exomes

AF:

0.0149

AC:

3615

AN:

242884

Hom.:

306

AF XY:

0.0113

AC XY:

1487

AN XY:

131674

show subpopulations

Gnomad AFR exome

AF:

0.201

Gnomad AMR exome

AF:

0.0117

Gnomad ASJ exome

AF:

0.00106

Gnomad EAS exome

AF:

0.0000561

Gnomad SAS exome

AF:

0.000551

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000569

Gnomad OTH exome

AF:

0.00738

GnomAD4 exome

AF:

0.00589

AC:

8556

AN:

1452602

Hom.:

720

Cov.:

AF XY:

0.00510

AC XY:

3679

AN XY:

721468

show subpopulations

Gnomad4 AFR exome

AF:

0.198

Gnomad4 AMR exome

AF:

0.0127

Gnomad4 ASJ exome

AF:

0.00101

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.000506

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000419

Gnomad4 OTH exome

AF:

0.0140

GnomAD4 genome

AF:

0.0571

AC:

8686

AN:

152194

Hom.:

796

Cov.:

AF XY:

0.0547

AC XY:

4067

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.196

Gnomad4 AMR

AF:

0.0263

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000691

Gnomad4 OTH

AF:

0.0350

Alfa

AF:

0.0102

Hom.:

267

Bravo

AF:

0.0647

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.173

AC:

685

ESP6500EA

AF:

0.000720

AC:

ExAC

AF:

0.0173

AC:

2095

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Apr 10, 2023

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

46,XY sex reversal 9

Benign:1

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.25

T;T;T

Eigen

Benign

-0.14

Eigen_PC

Benign

0.028

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.91

D;.;D

MetaRNN

Benign

0.0016

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.6

L;.;.

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.0

N;N;N

REVEL

Benign

0.13

Sift

Benign

0.24

T;D;D

Sift4G

Benign

0.19

T;T;T

Polyphen

0.020

B;.;.

Vest4

0.17

MPC

0.11

ClinPred

0.033

GERP RS

6.0

Varity_R

0.054

gMVP

0.33

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