Variant 16-88526863-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_153813.3(ZFPM1):c.452C>T(p.Thr151Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000774 in 1,576,266 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000066 ( 0 hom. )

Consequence

ZFPM1
NM_153813.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.61

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=0.009859294).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZFPM1	NM_153813.3 linkuse as main transcript	c.452C>T	p.Thr151Met	missense_variant	5/10	ENST00000319555.8
ZFPM1-AS1	NR_148997.1 linkuse as main transcript	n.289+3579G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZFPM1	ENST00000319555.8 linkuse as main transcript	c.452C>T	p.Thr151Met	missense_variant	5/10	1	NM_153813.3	P1
ZFPM1-AS1	ENST00000563243.1 linkuse as main transcript	n.289+3579G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

151656

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000580

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000129

AC:

AN:

194194

Hom.:

AF XY:

0.000144

AC XY:

AN XY:

104304

show subpopulations

Gnomad AFR exome

AF:

0.000691

Gnomad AMR exome

AF:

0.000441

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000120

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000121

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000660

AC:

AN:

1424492

Hom.:

Cov.:

AF XY:

0.0000766

AC XY:

AN XY:

705042

show subpopulations

Gnomad4 AFR exome

AF:

0.00128

Gnomad4 AMR exome

AF:

0.000423

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000862

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000137

Gnomad4 OTH exome

AF:

0.000170

GnomAD4 genome

AF:

0.000184

AC:

AN:

151774

Hom.:

Cov.:

AF XY:

0.000189

AC XY:

AN XY:

74162

show subpopulations

Gnomad4 AFR

AF:

0.000603

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000164

Hom.:

Bravo

AF:

0.000162

ExAC

AF:

0.0000589

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

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 01, 2021

The c.452C>T (p.T151M) alteration is located in exon 5 (coding exon 5) of the ZFPM1 gene. This alteration results from a C to T substitution at nucleotide position 452, causing the threonine (T) at amino acid position 151 to be replaced by a methionine (M). 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

0.063

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.81

Cadd

Benign

6.7

Dann

Uncertain

0.98

DEOGEN2

Benign

0.18

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.31

M_CAP

Benign

0.0096

MetaRNN

Benign

0.0099

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.065

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.77

REVEL

Benign

0.017

Sift

Benign

0.26

Sift4G

Benign

0.25

Polyphen

0.066

Vest4

0.10

MVP

0.13

MPC

0.25

ClinPred

0.011

GERP RS

-5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.019

gMVP

0.34

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