rs11993776

chr8-105801290-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_012082.4(ZFPM2):c.1208C>G(p.Ala403Gly) variant causes a missense change. The variant allele was found at a frequency of 0.109 in 1,613,686 control chromosomes in the GnomAD database, including 13,171 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 0.18 (3722 hom., cov: 32)
  • Exomes 𝑓: 0.10 (9449 hom.)
• Consequence: ZFPM2 NM_012082.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 4.12

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0036206841).
• BP6: Variant 8-105801290-C-G is Benign according to our data. Variant chr8-105801290-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 260170.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZFPM2	NM_012082.4	c.1208C>G	p.Ala403Gly	missense_variant	8/8	ENST00000407775.7
ZFPM2-AS1	NR_125797.1	n.191-2848G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZFPM2	ENST00000407775.7	c.1208C>G	p.Ala403Gly	missense_variant	8/8	1	NM_012082.4	P1
ZFPM2-AS1	ENST00000520433.5	n.212-2848G>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26745 AN: 151892 Hom.: 3699 Cov.: 32

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.0685

Gnomad FIN AF: 0.0686

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0913

Gnomad OTH AF: 0.160

GnomAD3 exomes AF: 0.110 AC: 27377 AN: 249044 Hom.: 2301 AF XY: 0.105 AC XY: 14137 AN XY: 135108

Gnomad AFR exome AF: 0.394

Gnomad AMR exome AF: 0.0780

Gnomad ASJ exome AF: 0.112

Gnomad EAS exome AF: 0.129

Gnomad SAS exome AF: 0.0817

Gnomad FIN exome AF: 0.0799

Gnomad NFE exome AF: 0.0910

Gnomad OTH exome AF: 0.109

GnomAD4 exome AF: 0.102 AC: 148490 AN: 1461676 Hom.: 9449 Cov.: 32 AF XY: 0.0996 AC XY: 72417 AN XY: 727120

Gnomad4 AFR exome AF: 0.393

Gnomad4 AMR exome AF: 0.0824

Gnomad4 ASJ exome AF: 0.113

Gnomad4 EAS exome AF: 0.163

Gnomad4 SAS exome AF: 0.0778

Gnomad4 FIN exome AF: 0.0806

Gnomad4 NFE exome AF: 0.0931

Gnomad4 OTH exome AF: 0.119

GnomAD4 genome AF: 0.176 AC: 26827 AN: 152010 Hom.: 3722 Cov.: 32 AF XY: 0.172 AC XY: 12758 AN XY: 74284

Gnomad4 AFR AF: 0.388

Gnomad4 AMR AF: 0.132

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.138

Gnomad4 SAS AF: 0.0682

Gnomad4 FIN AF: 0.0686

Gnomad4 NFE AF: 0.0913

Gnomad4 OTH AF: 0.164

Alfa AF: 0.106 Hom.: 845

Bravo AF: 0.190

TwinsUK AF: 0.0984 AC: 365

ALSPAC AF: 0.0939 AC: 362

ESP6500AA AF: 0.357 AC: 1423

ESP6500EA AF: 0.0941 AC: 787

ExAC AF: 0.115 AC: 13842

Asia WGS AF: 0.145 AC: 505 AN: 3478

EpiCase AF: 0.0911

EpiControl AF: 0.0904

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

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 04, 2023	- -
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 31, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 13, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.74
Cadd	Benign	12
Dann	Benign	0.72
DEOGEN2	Benign	0.13	T;T;T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.26	T;.;T
MetaRNN	Benign	0.0036	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-1.9	N;.;.
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	0.030	N;N;N
REVEL	Benign	0.17
Sift	Benign	1.0	T;T;T
Sift4G	Benign	0.87	T;T;T
Polyphen		0.0	B;.;.
Vest4		0.019
MPC		0.097
ClinPred		0.0021	T
GERP RS		4.0
Varity_R		0.040
gMVP		0.25

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: rs11993776; hg19: chr8-106813518; COSMIC: COSV65873817;