Variant 16-88486034-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000319555.8(ZFPM1):c.136C>A(p.Pro46Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00116 in 1,611,880 control chromosomes in the GnomAD database, including 5 homozygotes. 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 0.00074 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0012 ( 5 hom. )

Consequence

ZFPM1
ENST00000319555.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.308

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011256993).

BS2

High Homozygotes in GnomAdExome4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZFPM1	NM_153813.3 linkuse as main transcript	c.136C>A	p.Pro46Thr	missense_variant	2/10	ENST00000319555.8	NP_722520.2
ZFPM1	XM_011522912.3 linkuse as main transcript	c.274C>A	p.Pro92Thr	missense_variant	2/10		XP_011521214.1
ZFPM1	XM_011522914.3 linkuse as main transcript	c.235C>A	p.Pro79Thr	missense_variant	2/10		XP_011521216.1
ZFPM1	XM_047433667.1 linkuse as main transcript	c.183C>A	p.Leu61=	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.136C>A	p.Pro46Thr	missense_variant	2/10	1	NM_153813.3	ENSP00000326630	P1

Frequencies

GnomAD3 genomes

AF:

0.000736

AC:

112

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000289

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00132

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000647

AC:

159

AN:

245832

Hom.:

AF XY:

0.000628

AC XY:

AN XY:

133764

show subpopulations

Gnomad AFR exome

AF:

0.000385

Gnomad AMR exome

AF:

0.0000877

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000363

Gnomad FIN exome

AF:

0.0000472

Gnomad NFE exome

AF:

0.00122

Gnomad OTH exome

AF:

0.000499

GnomAD4 exome

AF:

0.00120

AC:

1750

AN:

1459516

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

800

AN XY:

726024

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.000192

Gnomad4 NFE exome

AF:

0.00149

Gnomad4 OTH exome

AF:

0.000830

GnomAD4 genome

AF:

0.000735

AC:

112

AN:

152364

Hom.:

Cov.:

AF XY:

0.000698

AC XY:

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.000457

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00132

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00108

Hom.:

Bravo

AF:

0.000737

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.000457

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.000654

AC:

EpiCase

AF:

0.00164

EpiControl

AF:

0.00137

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

Sep 17, 2021

The c.136C>A (p.P46T) alteration is located in exon 2 (coding exon 2) of the ZFPM1 gene. This alteration results from a C to A substitution at nucleotide position 136, causing the proline (P) at amino acid position 46 to be replaced by a threonine (T). 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

0.066

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.62

DANN

Benign

0.87

DEOGEN2

Benign

0.22

T;T;.;.

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.73

T;T;T;T

M_CAP

Benign

0.0067

MetaRNN

Benign

0.011

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

M;.;.;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.2

N;.;.;.

REVEL

Benign

0.033

Sift

Benign

0.32

T;.;.;.

Sift4G

Benign

0.079

T;D;D;D

Polyphen

0.44

B;.;.;.

Vest4

0.13

MVP

0.24

MPC

0.26

ClinPred

0.0037

GERP RS

-1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.035

gMVP

0.28

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