Variant 16-88485962-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000319555.8(ZFPM1):c.64A>G(p.Arg22Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 1,612,020 control chromosomes in the GnomAD database, including 141,489 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 19371 hom., cov: 33)

Exomes 𝑓: 0.40 ( 122118 hom. )

Consequence

ZFPM1
ENST00000319555.8 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.01

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.066438E-6).

BP6

Variant 16-88485962-A-G is Benign according to our data. Variant chr16-88485962-A-G is described in ClinVar as [Benign]. Clinvar id is 1224704.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZFPM1	NM_153813.3 linkuse as main transcript	c.64A>G	p.Arg22Gly	missense_variant	2/10	ENST00000319555.8	NP_722520.2
ZFPM1	XM_011522912.3 linkuse as main transcript	c.202A>G	p.Arg68Gly	missense_variant	2/10		XP_011521214.1
ZFPM1	XM_011522914.3 linkuse as main transcript	c.163A>G	p.Arg55Gly	missense_variant	2/10		XP_011521216.1
ZFPM1	XM_047433667.1 linkuse as main transcript	c.111A>G	p.Pro37=	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.64A>G	p.Arg22Gly	missense_variant	2/10	1	NM_153813.3	ENSP00000326630	P1

Frequencies

GnomAD3 genomes

AF:

0.484

AC:

73592

AN:

151998

Hom.:

19316

Cov.:

show subpopulations

Gnomad AFR

AF:

0.699

Gnomad AMI

AF:

0.340

Gnomad AMR

AF:

0.503

Gnomad ASJ

AF:

0.370

Gnomad EAS

AF:

0.500

Gnomad SAS

AF:

0.459

Gnomad FIN

AF:

0.371

Gnomad MID

AF:

0.468

Gnomad NFE

AF:

0.376

Gnomad OTH

AF:

0.456

GnomAD3 exomes

AF:

0.449

AC:

111662

AN:

248584

Hom.:

26916

AF XY:

0.437

AC XY:

58971

AN XY:

134954

show subpopulations

Gnomad AFR exome

AF:

0.707

Gnomad AMR exome

AF:

0.625

Gnomad ASJ exome

AF:

0.366

Gnomad EAS exome

AF:

0.492

Gnomad SAS exome

AF:

0.454

Gnomad FIN exome

AF:

0.376

Gnomad NFE exome

AF:

0.374

Gnomad OTH exome

AF:

0.409

GnomAD4 exome

AF:

0.402

AC:

586312

AN:

1459904

Hom.:

122118

Cov.:

AF XY:

0.401

AC XY:

291031

AN XY:

726232

show subpopulations

Gnomad4 AFR exome

AF:

0.708

Gnomad4 AMR exome

AF:

0.612

Gnomad4 ASJ exome

AF:

0.366

Gnomad4 EAS exome

AF:

0.513

Gnomad4 SAS exome

AF:

0.459

Gnomad4 FIN exome

AF:

0.384

Gnomad4 NFE exome

AF:

0.376

Gnomad4 OTH exome

AF:

0.417

GnomAD4 genome

AF:

0.485

AC:

73711

AN:

152116

Hom.:

19371

Cov.:

AF XY:

0.484

AC XY:

36014

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.699

Gnomad4 AMR

AF:

0.503

Gnomad4 ASJ

AF:

0.370

Gnomad4 EAS

AF:

0.500

Gnomad4 SAS

AF:

0.459

Gnomad4 FIN

AF:

0.371

Gnomad4 NFE

AF:

0.376

Gnomad4 OTH

AF:

0.461

Alfa

AF:

0.398

Hom.:

21508

Bravo

AF:

0.509

TwinsUK

AF:

0.373

AC:

1382

ALSPAC

AF:

0.365

AC:

1408

ESP6500AA

AF:

0.691

AC:

3033

ESP6500EA

AF:

0.375

AC:

3225

ExAC

AF:

0.447

AC:

54105

Asia WGS

AF:

0.513

AC:

1789

AN:

3478

EpiCase

AF:

0.381

EpiControl

AF:

0.379

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 19, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.048

BayesDel_addAF

Benign

-0.87

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.0030

DANN

Benign

0.23

DEOGEN2

Benign

0.10

T;T;.;.

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.0054

LIST_S2

Benign

0.32

T;T;T;T

MetaRNN

Benign

0.0000011

T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.49

N;.;.;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.40

PROVEAN

Benign

1.1

N;.;.;.

REVEL

Benign

0.012

Sift

Benign

0.92

T;.;.;.

Sift4G

Benign

0.54

T;T;T;T

Polyphen

0.0

B;.;.;.

Vest4

0.067

MPC

0.28

ClinPred

0.0019

GERP RS

-5.4

Varity_R

0.037

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