16-88485962-A-T

Variant names:

• chr16-88485962-A-T
• rs3751673
• NM_153813.3:c.64A>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_153813.3(ZFPM1):​c.64A>T​(p.Arg22*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZFPM1 NM_153813.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 27 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.64A>T	p.Arg22*	stop_gained	Exon 2 of 10	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.64A>T	p.Arg22*	stop_gained	Exon 2 of 10	ENSP00000326630.2	Q8IX07
	ZFPM1	ENST00000569086.5	TSL:2	c.64A>T	p.Arg22*	stop_gained	Exon 2 of 6	ENSP00000482796.1	A0A087WZP1
	ZFPM1	ENST00000562437.2	TSL:2	c.64A>T	p.Arg22*	stop_gained	Exon 2 of 5	ENSP00000480412.1	A0A087WWQ0

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 46

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	23
DANN	Uncertain	0.98
Eigen	Benign	-0.68
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.039	N
PhyloP100		-1.0
Vest4		0.68
GERP RS		-5.4
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.2

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: rs3751673; hg19: chr16-88552370;