rs182216711

chr8-105788814-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 4.96

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007355273).
• 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. This position pass quality control queck.
• BS2: High AC in GnomAd at 407 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZFPM2	NM_012082.4	c.629G>C	p.Ser210Thr	missense_variant	6/8	ENST00000407775.7
ZFPM2-AS1	NR_125797.1	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	c.629G>C	p.Ser210Thr	missense_variant	6/8	1	NM_012082.4	P1
ZFPM2-AS1	ENST00000520433.5	n.330-6331C>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00267 AC: 407 AN: 152184 Hom.: 0 Cov.: 32

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.: 1 AF XY: 0.00219 AC XY: 296 AN XY: 135188

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.: 8 Cov.: 31 AF XY: 0.00310 AC XY: 2257 AN XY: 727126

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.: 0 Cov.: 32 AF XY: 0.00236 AC XY: 176 AN XY: 74466

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.: 0

Bravo AF: 0.00354

TwinsUK AF: 0.00297 AC: 11

ALSPAC AF: 0.00182 AC: 7

ESP6500AA AF: 0.000250 AC: 1

ESP6500EA AF: 0.00430 AC: 36

ExAC AF: 0.00206 AC: 249

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00349

EpiControl AF: 0.00267

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

46,XY sex reversal 9 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 18, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2023

ZFPM2: BP4, BS1, BS2 -

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	T
BayesDel_noAF	Benign	-0.58
Cadd	Benign	23
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	D
LIST_S2	Benign	0.78	T;.;T
MetaRNN	Benign	0.0074	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;.;.
MutationTaster	Benign	0.93	D;D;D;D
PrimateAI	Uncertain	0.55	T
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	T
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

Other links and lift over

dbSNP: rs182216711; hg19: chr8-106801042;