rs182216711

Positions:

chr8-105788814-G-C

Variant summary

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

The NM_012082.4(ZFPM2):c.629G>C(p.Ser210Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00321 in 1,613,990 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0033 ( 8 hom. )

Consequence

ZFPM2
NM_012082.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 4.96

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=0.007355273).

BP6

Variant 8-105788814-G-C is Benign according to our data. Variant chr8-105788814-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 260179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-105788814-G-C is described in Lovd as [Likely_pathogenic]. Variant chr8-105788814-G-C is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00267 (407/152302) while in subpopulation AMR AF= 0.00869 (133/15304). AF 95% confidence interval is 0.00749. There are 0 homozygotes in gnomad4. There are 176 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 407 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZFPM2	NM_012082.4 linkuse as main transcript	c.629G>C	p.Ser210Thr	missense_variant	6/8	ENST00000407775.7
ZFPM2-AS1	NR_125797.1 linkuse as main transcript	n.309-6331C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZFPM2	ENST00000407775.7 linkuse as main transcript	c.629G>C	p.Ser210Thr	missense_variant	6/8	1	NM_012082.4	P1	Q8WW38-1
ZFPM2-AS1	ENST00000520433.5 linkuse as main transcript	n.330-6331C>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00267

AC:

407

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00870

Gnomad ASJ

AF:

0.00374

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00318

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00232

AC:

579

AN:

249184

Hom.:

AF XY:

0.00219

AC XY:

296

AN XY:

135188

show subpopulations

Gnomad AFR exome

AF:

0.000904

Gnomad AMR exome

AF:

0.00466

Gnomad ASJ exome

AF:

0.00278

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.000650

Gnomad NFE exome

AF:

0.00300

Gnomad OTH exome

AF:

0.00314

GnomAD4 exome

AF:

0.00326

AC:

4772

AN:

1461688

Hom.:

Cov.:

AF XY:

0.00310

AC XY:

2257

AN XY:

727126

show subpopulations

Gnomad4 AFR exome

AF:

0.000806

Gnomad4 AMR exome

AF:

0.00534

Gnomad4 ASJ exome

AF:

0.00367

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.000562

Gnomad4 NFE exome

AF:

0.00369

Gnomad4 OTH exome

AF:

0.00402

GnomAD4 genome

AF:

0.00267

AC:

407

AN:

152302

Hom.:

Cov.:

AF XY:

0.00236

AC XY:

176

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.000722

Gnomad4 AMR

AF:

0.00869

Gnomad4 ASJ

AF:

0.00374

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00318

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00286

Hom.:

Bravo

AF:

0.00354

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.000250

AC:

ESP6500EA

AF:

0.00430

AC:

ExAC

AF:

0.00206

AC:

249

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00349

EpiControl

AF:

0.00267

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Apr 21, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2024	ZFPM2: BP4, BS1, BS2 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

46,XY sex reversal 9

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 18, 2024

- -

46,XY sex reversal 3

Benign:1

Benign, no assertion criteria provided

research

Reproductive Development, Murdoch Childrens Research Institute

Aug 26, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.78

DEOGEN2

Benign

0.14

T;T;T

Eigen

Benign

-0.17

Eigen_PC

Benign

0.096

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.78

T;.;T

MetaRNN

Benign

0.0074

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;.;.

MutationTaster

Benign

0.93

D;D;D;D

PrimateAI

Uncertain

0.55

PROVEAN

Benign

0.29

N;N;N

REVEL

Benign

0.059

Sift

Benign

1.0

T;T;T

Sift4G

Benign

0.90

T;T;T

Polyphen

0.013

B;.;.

Vest4

0.53

MVP

0.53

MPC

0.089

ClinPred

0.0086

GERP RS

5.6

Varity_R

0.13

gMVP

0.21

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