NM_153813.3:c.282G>T

Variant names:

• chr16-88514400-G-T
• rs769825796
• NM_153813.3:c.282G>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_153813.3(ZFPM1):​c.282G>T​(p.Pro94Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000708 in 1,412,406 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P94P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: ZFPM1 NM_153813.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28
• Publications: 0 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-AS1 (HGNC:55351): (ZFPM1 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP7: Synonymous conserved (PhyloP=1.28 with no splicing effect.

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.282G>T	p.Pro94Pro	synonymous	Exon 4 of 10	NP_722520.2	Q8IX07
	ZFPM1-AS1	NR_148997.1		n.390-1097C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFPM1	ENST00000319555.8	TSL:1 MANE Select	c.282G>T	p.Pro94Pro	synonymous	Exon 4 of 10	ENSP00000326630.2	Q8IX07
	ZFPM1	ENST00000569086.5	TSL:2	c.282G>T	p.Pro94Pro	synonymous	Exon 4 of 6	ENSP00000482796.1	A0A087WZP1
	ZFPM1	ENST00000562437.2	TSL:2	c.282G>T	p.Pro94Pro	synonymous	Exon 4 of 5	ENSP00000480412.1	A0A087WWQ0

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.08e-7 AC: 1 AN: 1412406 Hom.: 0 Cov.: 32 AF XY: 0.00000143 AC XY: 1 AN XY: 698112

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32394

American (AMR) AF: 0.00 AC: 0 AN: 37794

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25282

East Asian (EAS) AF: 0.00 AC: 0 AN: 37016

South Asian (SAS) AF: 0.00 AC: 0 AN: 80284

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48266

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5694

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1087170

Other (OTH) AF: 0.0000171 AC: 1 AN: 58506

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.1
DANN	Benign	0.86
PhyloP100		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs769825796; hg19: chr16-88580808;