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GeneBe

16-88526888-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_153813.3(ZFPM1):c.477C>T(p.Ala159=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00133 in 1,579,884 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0072 ( 15 hom., cov: 33)
Exomes 𝑓: 0.00071 ( 10 hom. )

Consequence

ZFPM1
NM_153813.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -6.39
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-AS1 (HGNC:55351): (ZFPM1 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 16-88526888-C-T is Benign according to our data. Variant chr16-88526888-C-T is described in ClinVar as [Benign]. Clinvar id is 786298.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-6.39 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00719 (1094/152168) while in subpopulation AFR AF= 0.0248 (1031/41514). AF 95% confidence interval is 0.0236. There are 15 homozygotes in gnomad4. There are 495 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 15 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ZFPM1NM_153813.3 linkuse as main transcriptc.477C>T p.Ala159= synonymous_variant 5/10 ENST00000319555.8
ZFPM1-AS1NR_148997.1 linkuse as main transcriptn.289+3554G>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ZFPM1ENST00000319555.8 linkuse as main transcriptc.477C>T p.Ala159= synonymous_variant 5/101 NM_153813.3 P1
ZFPM1-AS1ENST00000563243.1 linkuse as main transcriptn.289+3554G>A intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00720
AC:
1094
AN:
152050
Hom.:
15
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0249
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00282
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.00525
GnomAD3 exomes
AF:
0.00159
AC:
310
AN:
195390
Hom.:
4
AF XY:
0.00108
AC XY:
113
AN XY:
104832
show subpopulations
Gnomad AFR exome
AF:
0.0229
Gnomad AMR exome
AF:
0.000979
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000159
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000722
Gnomad OTH exome
AF:
0.000798
GnomAD4 exome
AF:
0.000706
AC:
1008
AN:
1427716
Hom.:
10
Cov.:
36
AF XY:
0.000576
AC XY:
407
AN XY:
706852
show subpopulations
Gnomad4 AFR exome
AF:
0.0247
Gnomad4 AMR exome
AF:
0.00121
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000111
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000493
Gnomad4 OTH exome
AF:
0.00137
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00719
AC:
1094
AN:
152168
Hom.:
15
Cov.:
33
AF XY:
0.00665
AC XY:
495
AN XY:
74404
show subpopulations
Gnomad4 AFR
AF:
0.0248
Gnomad4 AMR
AF:
0.00281
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.00520
Alfa
AF:
0.00271
Hom.:
0
Bravo
AF:
0.00810
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.76
Cadd
Benign
0.29
Dann
Benign
0.85
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs114240624; hg19: chr16-88593296; API