16-88489132-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_153813.3(ZFPM1):c.247G>A(p.Gly83Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000267 in 1,608,078 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 0.00016 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: ZFPM1 NM_153813.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.649

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]

ACMG classification

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=0.013207436).
• BP6: Variant 16-88489132-G-A is Benign according to our data. Variant chr16-88489132-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2454927.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZFPM1	NM_153813.3	c.247G>A	p.Gly83Ser	missense_variant	3/10	ENST00000319555.8
ZFPM1	XM_011522912.3	c.385G>A	p.Gly129Ser	missense_variant	3/10
ZFPM1	XM_011522914.3	c.346G>A	p.Gly116Ser	missense_variant	3/10
ZFPM1	XM_047433667.1	c.294G>A	p.Arg98=	synonymous_variant	3/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZFPM1	ENST00000319555.8	c.247G>A	p.Gly83Ser	missense_variant	3/10	1	NM_153813.3	P1

Frequencies

GnomAD3 genomes AF: 0.000158 AC: 24 AN: 152260 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.000410

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000392

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: 0.00

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.0000552 AC: 13 AN: 235470 Hom.: 0 AF XY: 0.0000467 AC XY: 6 AN XY: 128350

Gnomad AFR exome AF: 0.000550

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000169

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000131 AC: 19 AN: 1455700 Hom.: 0 Cov.: 31 AF XY: 0.00000967 AC XY: 7 AN XY: 723952

Gnomad4 AFR exome AF: 0.000181

Gnomad4 AMR exome AF: 0.0000678

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000701

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000666

GnomAD4 genome AF: 0.000158 AC: 24 AN: 152378 Hom.: 0 Cov.: 34 AF XY: 0.000188 AC XY: 14 AN XY: 74510

Gnomad4 AFR AF: 0.000409

Gnomad4 AMR AF: 0.000392

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.000215

ExAC AF: 0.0000748 AC: 9

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 09, 2023

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	0.083
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.68
Cadd	Benign	0.071
Dann	Benign	0.90
DEOGEN2	Benign	0.17	T;T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.53	T;T;T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.013	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.90	L;.;.
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.70	N;.;.
REVEL	Benign	0.017
Sift	Benign	0.14	T;.;.
Sift4G	Benign	0.54	T;T;T
Polyphen		0.010	B;.;.
Vest4		0.15
MutPred		0.15		Gain of phosphorylation at G83 (P = 0.0023);Gain of phosphorylation at G83 (P = 0.0023);Gain of phosphorylation at G83 (P = 0.0023);
MVP		0.076
MPC		0.22
ClinPred		0.023	T
GERP RS		-2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.040
gMVP		0.18

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

Other links and lift over

dbSNP: rs558530910; hg19: chr16-88555540;