16-88462372-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153813.3(ZFPM1):c.40+8694T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 152,200 control chromosomes in the GnomAD database, including 14,263 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 0.41 (14263 hom., cov: 34)
• Consequence: ZFPM1 NM_153813.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.481

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZFPM1	NM_153813.3	c.40+8694T>C		intron_variant		ENST00000319555.8
ZFPM1	XM_011522914.3	c.139+10434T>C		intron_variant
ZFPM1	XM_047433667.1	c.87+10434T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZFPM1	ENST00000319555.8	c.40+8694T>C		intron_variant		1	NM_153813.3	P1

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62936 AN: 152082 Hom.: 14241 Cov.: 34

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.491

Gnomad SAS AF: 0.474

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.380

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

GnomAD4 genome AF: 0.414 AC: 63007 AN: 152200 Hom.: 14263 Cov.: 34 AF XY: 0.415 AC XY: 30880 AN XY: 74406

Gnomad4 AFR AF: 0.587

Gnomad4 AMR AF: 0.437

Gnomad4 ASJ AF: 0.308

Gnomad4 EAS AF: 0.490

Gnomad4 SAS AF: 0.473

Gnomad4 FIN AF: 0.304

Gnomad4 NFE AF: 0.318

Gnomad4 OTH AF: 0.385

Alfa AF: 0.374 Hom.: 3804

Bravo AF: 0.432

Asia WGS AF: 0.482 AC: 1678 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	4.5
Dann	Benign	0.56

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

Publications

LitVar

Other links and lift over

dbSNP: rs904790; hg19: chr16-88528780; COSMIC: COSV60320962;