Genetic Variant ZFPM1:p.Pro82Leu (chr16-88489130-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_153813.3(ZFPM1):c.245C>T(p.Pro82Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000755 in 1,456,286 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000076 ( 0 hom. )

Consequence

ZFPM1
NM_153813.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0500

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1358161).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFPM1	NM_153813.3 link	c.245C>T	p.Pro82Leu	missense_variant	Exon 3 of 10	ENST00000319555.8	NP_722520.2	Q8IX07
ZFPM1	XM_011522912.3 link	c.383C>T	p.Pro128Leu	missense_variant	Exon 3 of 10		XP_011521214.1
ZFPM1	XM_011522914.3 link	c.344C>T	p.Pro115Leu	missense_variant	Exon 3 of 10		XP_011521216.1
ZFPM1	XM_047433667.1 link	c.292C>T	p.Arg98Trp	missense_variant	Exon 3 of 9		XP_047289623.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFPM1	ENST00000319555.8 link	c.245C>T	p.Pro82Leu	missense_variant	Exon 3 of 10	1	NM_153813.3	ENSP00000326630.2		Q8IX07

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000844

AC:

AN:

236946

Hom.:

AF XY:

0.00000774

AC XY:

AN XY:

129198

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000190

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000755

AC:

AN:

1456286

Hom.:

Cov.:

AF XY:

0.00000552

AC XY:

AN XY:

724344

show subpopulations

Gnomad4 AFR exome

AF:

0.0000602

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000233

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000631

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000508

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 26, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.245C>T (p.P82L) alteration is located in exon 3 (coding exon 3) of the ZFPM1 gene. This alteration results from a C to T substitution at nucleotide position 245, causing the proline (P) at amino acid position 82 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

T;T;.

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.092

LIST_S2

Benign

0.70

T;T;T

M_CAP

Benign

0.0048

MetaRNN

Benign

0.14

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.90

L;.;.

PrimateAI

Benign

0.46

PROVEAN

Benign

-2.0

N;.;.

REVEL

Benign

0.10

Sift

Uncertain

0.0080

D;.;.

Sift4G

Benign

0.15

T;D;D

Polyphen

0.80

P;.;.

Vest4

0.20

MutPred

0.18

Gain of solvent accessibility (P = 0.0149);Gain of solvent accessibility (P = 0.0149);Gain of solvent accessibility (P = 0.0149);

MVP

0.42

MPC

0.22

ClinPred

0.18

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.066

gMVP

0.17

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over