Variant 16-88528103-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000319555.8(ZFPM1):c.577G>A(p.Glu193Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000272 in 1,582,148 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000086 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

ZFPM1
ENST00000319555.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.28

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:

ZFPM1-AS1 (HGNC:55351): (ZFPM1 antisense RNA 1)

ZFPM1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06481844).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFPM1	NM_153813.3 linkuse as main transcript	c.577G>A	p.Glu193Lys	missense_variant	6/10	ENST00000319555.8	NP_722520.2
ZFPM1-AS1	NR_148997.1 linkuse as main transcript	n.289+2339C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFPM1	ENST00000319555.8 linkuse as main transcript	c.577G>A	p.Glu193Lys	missense_variant	6/10	1	NM_153813.3	ENSP00000326630	P1
ZFPM1-AS1	ENST00000563243.1 linkuse as main transcript	n.289+2339C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000856

AC:

AN:

151902

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

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:

0.0000147

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.0000253

AC:

AN:

197690

Hom.:

AF XY:

0.0000374

AC XY:

AN XY:

106984

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000679

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:

0.0000237

Gnomad OTH exome

AF:

0.000196

GnomAD4 exome

AF:

0.0000210

AC:

AN:

1430128

Hom.:

Cov.:

AF XY:

0.0000254

AC XY:

AN XY:

708636

show subpopulations

Gnomad4 AFR exome

AF:

0.0000912

Gnomad4 AMR exome

AF:

0.000173

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000201

Gnomad4 NFE exome

AF:

0.0000128

Gnomad4 OTH exome

AF:

0.0000846

GnomAD4 genome

AF:

0.0000855

AC:

AN:

152020

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000155

ExAC

AF:

0.00000837

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 06, 2021

The c.577G>A (p.E193K) alteration is located in exon 6 (coding exon 6) of the ZFPM1 gene. This alteration results from a G to A substitution at nucleotide position 577, causing the glutamic acid (E) at amino acid position 193 to be replaced by a lysine (K). 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

0.082

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.64

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.54

M_CAP

Benign

0.025

MetaRNN

Benign

0.065

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

MutationTaster

Benign

0.86

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.5

REVEL

Benign

0.029

Sift

Benign

0.20

Sift4G

Benign

0.17

Polyphen

0.12

Vest4

0.20

MVP

0.43

MPC

0.24

ClinPred

0.052

GERP RS

3.5

Varity_R

0.057

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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