rs11995760

Variant names:

• chr8-105803289-C-T
• rs11995760
• NM_012082.4:c.3207C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-105803289-C-T
• chr8-105803289-C-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_012082.4(ZFPM2):​c.3207C>T​(p.His1069His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0404 in 1,594,158 control chromosomes in the GnomAD database, including 5,053 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (2412 hom., cov: 32)
  • Exomes 𝑓: 0.033 (2641 hom.)
• Consequence: ZFPM2 NM_012082.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.197
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 8-105803289-C-T is Benign according to our data. Variant chr8-105803289-C-T is described in ClinVar as Benign. ClinVar VariationId is 260178.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.197 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012082.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFPM2	NM_012082.4	MANE Select	c.3207C>T	p.His1069His	synonymous	Exon 8 of 8	NP_036214.2	Q8WW38-1
	ZFPM2	NM_001362836.2		c.3048C>T	p.His1016His	synonymous	Exon 7 of 7	NP_001349765.1
	ZFPM2	NM_001362837.2		c.2811C>T	p.His937His	synonymous	Exon 8 of 8	NP_001349766.1	E7ET52

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFPM2	ENST00000407775.7	TSL:1 MANE Select	c.3207C>T	p.His1069His	synonymous	Exon 8 of 8	ENSP00000384179.2	Q8WW38-1
	ZFPM2	ENST00000941376.1		c.3204C>T	p.His1068His	synonymous	Exon 8 of 8	ENSP00000611435.1
	ZFPM2	ENST00000517361.1	TSL:2	c.2811C>T	p.His937His	synonymous	Exon 6 of 6	ENSP00000428720.1	E7ET52

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17115 AN: 152026 Hom.: 2393 Cov.: 32

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0814

Gnomad ASJ AF: 0.0706

Gnomad EAS AF: 0.00792

Gnomad SAS AF: 0.0329

Gnomad FIN AF: 0.00424

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0217

Gnomad OTH AF: 0.0957

GnomAD2 exomes AF: 0.0472 AC: 11005 AN: 233362 AF XY: 0.0414

Gnomad AFR exome AF: 0.337

Gnomad AMR exome AF: 0.0436

Gnomad ASJ exome AF: 0.0747

Gnomad EAS exome AF: 0.00689

Gnomad FIN exome AF: 0.00432

Gnomad NFE exome AF: 0.0224

Gnomad OTH exome AF: 0.0417

GnomAD4 exome AF: 0.0328 AC: 47262 AN: 1442014 Hom.: 2641 Cov.: 32 AF XY: 0.0317 AC XY: 22644 AN XY: 714944

African (AFR) AF: 0.341 AC: 11185 AN: 32834

American (AMR) AF: 0.0473 AC: 2029 AN: 42924

Ashkenazi Jewish (ASJ) AF: 0.0712 AC: 1756 AN: 24676

East Asian (EAS) AF: 0.00464 AC: 183 AN: 39468

South Asian (SAS) AF: 0.0309 AC: 2552 AN: 82616

European-Finnish (FIN) AF: 0.00538 AC: 283 AN: 52628

Middle Eastern (MID) AF: 0.0433 AC: 244 AN: 5634

European-Non Finnish (NFE) AF: 0.0236 AC: 26009 AN: 1101810

Other (OTH) AF: 0.0508 AC: 3021 AN: 59424

GnomAD4 genome AF: 0.113 AC: 17179 AN: 152144 Hom.: 2412 Cov.: 32 AF XY: 0.109 AC XY: 8127 AN XY: 74390

African (AFR) AF: 0.332 AC: 13762 AN: 41462

American (AMR) AF: 0.0812 AC: 1241 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0706 AC: 245 AN: 3468

East Asian (EAS) AF: 0.00774 AC: 40 AN: 5166

South Asian (SAS) AF: 0.0321 AC: 155 AN: 4826

European-Finnish (FIN) AF: 0.00424 AC: 45 AN: 10608

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0217 AC: 1474 AN: 68010

Other (OTH) AF: 0.0952 AC: 201 AN: 2112

Alfa AF: 0.0576 Hom.: 2622

Bravo AF: 0.128

Asia WGS AF: 0.0670 AC: 234 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	46,XY sex reversal 9 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.39
DANN	Benign	0.80
PhyloP100		0.20
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11995760; hg19: chr8-106815517; COSMIC: COSV101023185;