Genetic Variant ZFPM1:p.Arg10Gln (chr16-88453667-G-A) – 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.29G>A(p.Arg10Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000158 in 1,200,278 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

ZFPM1
NM_153813.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.43

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:

Genome browser will be placed here

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=0.2290014).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFPM1	NM_153813.3 link	c.29G>A	p.Arg10Gln	missense_variant	Exon 1 of 10	ENST00000319555.8	NP_722520.2	Q8IX07
ZFPM1	XM_011522914.3 link	c.139+1729G>A		intron_variant	Intron 1 of 9		XP_011521216.1
ZFPM1	XM_047433667.1 link	c.87+1729G>A		intron_variant	Intron 1 of 8		XP_047289623.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFPM1	ENST00000319555.8 link	c.29G>A	p.Arg10Gln	missense_variant	Exon 1 of 10	1	NM_153813.3	ENSP00000326630.2		Q8IX07

Frequencies

GnomAD3 genomes

AF:

0.00000673

AC:

AN:

148540

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000150

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000171

AC:

AN:

1051738

Hom.:

Cov.:

AF XY:

0.0000156

AC XY:

AN XY:

514220

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000199

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000181

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000673

AC:

AN:

148540

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

72310

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000150

Gnomad4 OTH

AF:

0.00

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

Dec 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.29G>A (p.R10Q) alteration is located in exon 1 (coding exon 1) of the ZFPM1 gene. This alteration results from a G to A substitution at nucleotide position 29, causing the arginine (R) at amino acid position 10 to be replaced by a glutamine (Q). 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

Pathogenic

0.93

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.52

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

T;T;.;.

Eigen

Benign

0.095

Eigen_PC

Benign

0.014

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.74

T;T;T;T

M_CAP

Pathogenic

0.61

MetaRNN

Benign

0.23

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.4

L;.;.;.

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.82

N;.;.;.

REVEL

Benign

0.13

Sift

Uncertain

0.010

D;.;.;.

Sift4G

Uncertain

0.046

D;D;T;D

Polyphen

0.99

D;.;.;.

Vest4

0.12

MutPred

0.14

Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);

MVP

0.37

MPC

0.29

ClinPred

0.24

GERP RS

2.6

Varity_R

0.48

gMVP

0.50

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