rs182216711

Variant names:

• chr8-105788814-G-C
• rs182216711
• NM_012082.4:c.629G>C

Your query was ambiguous. Multiple possible variants found:

• chr8-105788814-G-C
• chr8-105788814-G-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_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. 13/21 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:6
• Conservation: PhyloP100: 4.96
• Publications: 13 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007355273).
• BP6: Variant 8-105788814-G-C is Benign according to our data. Variant chr8-105788814-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 260179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 407 Unknown,AD gene.

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.629G>C	p.Ser210Thr	missense	Exon 6 of 8	NP_036214.2	Q8WW38-1
	ZFPM2	NM_001362836.2		c.470G>C	p.Ser157Thr	missense	Exon 5 of 7	NP_001349765.1
	ZFPM2	NM_001362837.2		c.233G>C	p.Ser78Thr	missense	Exon 6 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.629G>C	p.Ser210Thr	missense	Exon 6 of 8	ENSP00000384179.2	Q8WW38-1
	ZFPM2	ENST00000511341.6	TSL:1	n.1369G>C		non_coding_transcript_exon	Exon 6 of 6
	ZFPM2	ENST00000941376.1		c.626G>C	p.Ser209Thr	missense	Exon 6 of 8	ENSP00000611435.1

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

GnomAD2 exomes AF: 0.00232 AC: 579 AN: 249184 AF XY: 0.00219

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 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

African (AFR) AF: 0.000806 AC: 27 AN: 33480

American (AMR) AF: 0.00534 AC: 239 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00367 AC: 96 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000812 AC: 7 AN: 86258

European-Finnish (FIN) AF: 0.000562 AC: 30 AN: 53402

Middle Eastern (MID) AF: 0.00416 AC: 24 AN: 5766

European-Non Finnish (NFE) AF: 0.00369 AC: 4106 AN: 1111850

Other (OTH) AF: 0.00402 AC: 243 AN: 60374

GnomAD4 genome AF: 0.00267 AC: 407 AN: 152302 Hom.: 0 Cov.: 32 AF XY: 0.00236 AC XY: 176 AN XY: 74466

African (AFR) AF: 0.000722 AC: 30 AN: 41564

American (AMR) AF: 0.00869 AC: 133 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00374 AC: 13 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10624

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00318 AC: 216 AN: 68018

Other (OTH) AF: 0.00473 AC: 10 AN: 2114

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

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	46,XY sex reversal 3 (1)
-	-	1	46,XY sex reversal 9 (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.17
Eigen_PC	Benign	0.096
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.78	T
MetaRNN	Benign	0.0074	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		5.0
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	0.29	N
REVEL	Benign	0.059
Sift	Benign	1.0	T
Sift4G	Benign	0.90	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
Mutation Taster		=89/11	polymorphism

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: rs182216711; hg19: chr8-106801042;