8-105561350-C-T

Position:

• chr8-105561350-C-T

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.302-13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.604 in 1,606,566 control chromosomes in the GnomAD database, including 298,307 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.68 (36535 hom., cov: 32)
  • Exomes 𝑓: 0.60 (261772 hom.)
• Consequence: ZFPM2 NM_012082.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.911

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 8-105561350-C-T is Benign according to our data. Variant chr8-105561350-C-T is described in ClinVar as [Benign]. Clinvar id is 260177.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-105561350-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFPM2	NM_012082.4	c.302-13C>T		intron_variant		ENST00000407775.7	NP_036214.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFPM2	ENST00000407775.7	c.302-13C>T		intron_variant		1	NM_012082.4	ENSP00000384179.2

Frequencies

GnomAD3 genomes AF: 0.679 AC: 103056 AN: 151884 Hom.: 36499 Cov.: 32

Gnomad AFR AF: 0.911

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.613

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.595

Gnomad SAS AF: 0.713

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.654

GnomAD3 exomes AF: 0.618 AC: 152047 AN: 245868 Hom.: 48011 AF XY: 0.621 AC XY: 82725 AN XY: 133294

Gnomad AFR exome AF: 0.917

Gnomad AMR exome AF: 0.564

Gnomad ASJ exome AF: 0.599

Gnomad EAS exome AF: 0.597

Gnomad SAS exome AF: 0.727

Gnomad FIN exome AF: 0.564

Gnomad NFE exome AF: 0.580

Gnomad OTH exome AF: 0.614

GnomAD4 exome AF: 0.596 AC: 867033 AN: 1454564 Hom.: 261772 Cov.: 30 AF XY: 0.599 AC XY: 433865 AN XY: 723860

Gnomad4 AFR exome AF: 0.923

Gnomad4 AMR exome AF: 0.565

Gnomad4 ASJ exome AF: 0.601

Gnomad4 EAS exome AF: 0.553

Gnomad4 SAS exome AF: 0.720

Gnomad4 FIN exome AF: 0.576

Gnomad4 NFE exome AF: 0.578

Gnomad4 OTH exome AF: 0.623

GnomAD4 genome AF: 0.679 AC: 103147 AN: 152002 Hom.: 36535 Cov.: 32 AF XY: 0.675 AC XY: 50127 AN XY: 74270

Gnomad4 AFR AF: 0.911

Gnomad4 AMR AF: 0.613

Gnomad4 ASJ AF: 0.616

Gnomad4 EAS AF: 0.595

Gnomad4 SAS AF: 0.711

Gnomad4 FIN AF: 0.572

Gnomad4 NFE AF: 0.579

Gnomad4 OTH AF: 0.658

Alfa AF: 0.595 Hom.: 46322

Bravo AF: 0.684

Asia WGS AF: 0.723 AC: 2510 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Apr 04, 2023	- -

46,XY sex reversal 9 Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 13, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Tetralogy of Fallot Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	9.9
DANN	Benign	0.66

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: rs3735953; hg19: chr8-106573578;