Variant 16-88485971-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The ENST00000319555.8(ZFPM1):c.73G>A(p.Val25Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000552 in 1,612,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

ZFPM1
ENST00000319555.8 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.102

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.02198428).

BP6

Variant 16-88485971-G-A is Benign according to our data. Variant chr16-88485971-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3334544.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZFPM1	NM_153813.3 linkuse as main transcript	c.73G>A	p.Val25Met	missense_variant	2/10	ENST00000319555.8	NP_722520.2
ZFPM1	XM_011522912.3 linkuse as main transcript	c.211G>A	p.Val71Met	missense_variant	2/10		XP_011521214.1
ZFPM1	XM_011522914.3 linkuse as main transcript	c.172G>A	p.Val58Met	missense_variant	2/10		XP_011521216.1
ZFPM1	XM_047433667.1 linkuse as main transcript	c.120G>A	p.Arg40=	synonymous_variant	2/9		XP_047289623.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFPM1	ENST00000319555.8 linkuse as main transcript	c.73G>A	p.Val25Met	missense_variant	2/10	1	NM_153813.3	ENSP00000326630	P1

Frequencies

GnomAD3 genomes

AF:

0.000217

AC:

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000651

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000481

AC:

AN:

249354

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

135408

show subpopulations

Gnomad AFR exome

AF:

0.000500

Gnomad AMR exome

AF:

0.000116

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000377

AC:

AN:

1460516

Hom.:

Cov.:

AF XY:

0.0000330

AC XY:

AN XY:

726576

show subpopulations

Gnomad4 AFR exome

AF:

0.000508

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000288

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

AF:

0.000223

AC:

AN:

152362

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.000673

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000230

Hom.:

Bravo

AF:

0.000268

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000578

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 08, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.9

DANN

Benign

0.64

DEOGEN2

Benign

0.13

T;T;.;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.049

LIST_S2

Benign

0.69

T;T;T;T

M_CAP

Benign

0.0084

MetaRNN

Benign

0.022

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.69

N;.;.;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.14

N;.;.;.

REVEL

Benign

0.029

Sift

Benign

0.13

T;.;.;.

Sift4G

Benign

0.12

T;T;T;T

Polyphen

0.0

B;.;.;.

Vest4

0.029

MVP

0.16

MPC

0.22

ClinPred

0.0082

GERP RS

0.62

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.2

Varity_R

0.027

gMVP

0.15

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