Variant 8-105318993-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_012082.4(ZFPM2):c.40+12C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0108 in 1,491,686 control chromosomes in the GnomAD database, including 114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0069 ( 2 hom., cov: 32)

Exomes 𝑓: 0.011 ( 112 hom. )

Consequence

ZFPM2
NM_012082.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.31

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:

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 (BayesDel_noAF=-0.53).

BP6

Variant 8-105318993-C-G is Benign according to our data. Variant chr8-105318993-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1558608.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00694 (1057/152196) while in subpopulation NFE AF= 0.0116 (790/67998). AF 95% confidence interval is 0.0109. There are 2 homozygotes in gnomad4. There are 498 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1057 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFPM2	NM_012082.4 linkuse as main transcript	c.40+12C>G		intron_variant		ENST00000407775.7	NP_036214.2
ZFPM2	NM_001362836.2 linkuse as main transcript	c.40+12C>G		intron_variant			NP_001349765.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFPM2	ENST00000407775.7 linkuse as main transcript	c.40+12C>G		intron_variant		1	NM_012082.4	ENSP00000384179	P1	Q8WW38-1
ZFPM2	ENST00000518180.1 linkuse as main transcript	n.479+72464C>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.00694

AC:

1056

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00200

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.00360

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.00898

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0116

Gnomad OTH

AF:

0.00479

GnomAD3 exomes

AF:

0.00610

AC:

727

AN:

119206

Hom.:

AF XY:

0.00624

AC XY:

403

AN XY:

64612

show subpopulations

Gnomad AFR exome

AF:

0.00132

Gnomad AMR exome

AF:

0.00170

Gnomad ASJ exome

AF:

0.00173

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00365

Gnomad FIN exome

AF:

0.00779

Gnomad NFE exome

AF:

0.0106

Gnomad OTH exome

AF:

0.00597

GnomAD4 exome

AF:

0.0113

AC:

15070

AN:

1339490

Hom.:

112

Cov.:

AF XY:

0.0110

AC XY:

7281

AN XY:

660926

show subpopulations

Gnomad4 AFR exome

AF:

0.00127

Gnomad4 AMR exome

AF:

0.00207

Gnomad4 ASJ exome

AF:

0.00139

Gnomad4 EAS exome

AF:

0.0000653

Gnomad4 SAS exome

AF:

0.00320

Gnomad4 FIN exome

AF:

0.00906

Gnomad4 NFE exome

AF:

0.0131

Gnomad4 OTH exome

AF:

0.00986

GnomAD4 genome

AF:

0.00694

AC:

1057

AN:

152196

Hom.:

Cov.:

AF XY:

0.00669

AC XY:

498

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.00200

Gnomad4 AMR

AF:

0.00359

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.00898

Gnomad4 NFE

AF:

0.0116

Gnomad4 OTH

AF:

0.00474

Alfa

AF:

0.00334

Hom.:

Bravo

AF:

0.00643

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

46,XY sex reversal 9

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 16, 2024

- -

Tetralogy of Fallot;C1857781:Diaphragmatic hernia 3;C4015129:46,XY sex reversal 9

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Apr 26, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.87

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