NM_153813.3:c.41-3083C>G

Variant names:

• chr16-88482856-C-G
• rs55637647
• NM_153813.3:c.41-3083C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153813.3(ZFPM1):​c.41-3083C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 152,160 control chromosomes in the GnomAD database, including 17,744 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.46 (17744 hom., cov: 33)
• Consequence: ZFPM1 NM_153813.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.362
• Publications: 12 publications found

Genes affected

ZFPM1 (HGNC:19762): (zinc finger protein, FOG family member 1) Enables RNA polymerase II-specific DNA-binding transcription factor binding activity and transcription corepressor activity. Involved in platelet formation; regulation of definitive erythrocyte differentiation; and regulation of gene expression. Part of transcription repressor complex. [provided by Alliance of Genome Resources, Apr 2022]

ZFPM1 Gene-Disease associations (from GenCC):

• congenital heart disease

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153813.3. 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
	ZFPM1	NM_153813.3	MANE Select	c.41-3083C>G		intron	N/A	NP_722520.2	Q8IX07

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFPM1	ENST00000319555.8	TSL:1 MANE Select	c.41-3083C>G		intron	N/A	ENSP00000326630.2	Q8IX07
	ZFPM1	ENST00000569086.5	TSL:2	c.41-3083C>G		intron	N/A	ENSP00000482796.1	A0A087WZP1
	ZFPM1	ENST00000562437.2	TSL:2	c.41-3083C>G		intron	N/A	ENSP00000480412.1	A0A087WWQ0

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70337 AN: 152042 Hom.: 17694 Cov.: 33

Gnomad AFR AF: 0.669

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.493

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.440

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.463 AC: 70450 AN: 152160 Hom.: 17744 Cov.: 33 AF XY: 0.460 AC XY: 34243 AN XY: 74382

African (AFR) AF: 0.670 AC: 27822 AN: 41526

American (AMR) AF: 0.486 AC: 7429 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 1171 AN: 3470

East Asian (EAS) AF: 0.492 AC: 2540 AN: 5158

South Asian (SAS) AF: 0.452 AC: 2178 AN: 4816

European-Finnish (FIN) AF: 0.300 AC: 3178 AN: 10598

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.364 AC: 24759 AN: 67986

Other (OTH) AF: 0.445 AC: 940 AN: 2112

Alfa AF: 0.428 Hom.: 1887

Bravo AF: 0.489

Asia WGS AF: 0.500 AC: 1738 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.31
PhyloP100		-0.36
RBP_binding_hub_radar		0.91
RBP_regulation_power_radar		2.2
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: rs55637647; hg19: chr16-88549264;