16-88489094-G-C

Position:

• chr16-88489094-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_153813.3(ZFPM1):​c.209G>C​(p.Gly70Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00191 in 1,613,016 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.010 (21 hom., cov: 34)
  • Exomes 𝑓: 0.0011 (21 hom.)
• Consequence: ZFPM1 NM_153813.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.676

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0024577081).
• BP6: Variant 16-88489094-G-C is Benign according to our data. Variant chr16-88489094-G-C is described in ClinVar as [Benign]. Clinvar id is 784346.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0101 (1543/152346) while in subpopulation AFR AF= 0.0347 (1444/41584). AF 95% confidence interval is 0.0332. There are 21 homozygotes in gnomad4. There are 692 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 21 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFPM1	NM_153813.3	c.209G>C	p.Gly70Ala	missense_variant	3/10	ENST00000319555.8	NP_722520.2
ZFPM1	XM_011522912.3	c.347G>C	p.Gly116Ala	missense_variant	3/10		XP_011521214.1
ZFPM1	XM_011522914.3	c.308G>C	p.Gly103Ala	missense_variant	3/10		XP_011521216.1
ZFPM1	XM_047433667.1	c.256G>C	p.Asp86His	missense_variant	3/9		XP_047289623.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFPM1	ENST00000319555.8	c.209G>C	p.Gly70Ala	missense_variant	3/10	1	NM_153813.3	ENSP00000326630.2

Frequencies

GnomAD3 genomes AF: 0.0101 AC: 1536 AN: 152228 Hom.: 21 Cov.: 34

Gnomad AFR AF: 0.0347

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00471

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00717

GnomAD3 exomes AF: 0.00257 AC: 638 AN: 247902 Hom.: 7 AF XY: 0.00193 AC XY: 260 AN XY: 134526

Gnomad AFR exome AF: 0.0358

Gnomad AMR exome AF: 0.00145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000719

Gnomad OTH exome AF: 0.00116

GnomAD4 exome AF: 0.00106 AC: 1542 AN: 1460670 Hom.: 21 Cov.: 31 AF XY: 0.000884 AC XY: 642 AN XY: 726634

Gnomad4 AFR exome AF: 0.0369

Gnomad4 AMR exome AF: 0.00157

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000104

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000378

Gnomad4 OTH exome AF: 0.00288

GnomAD4 genome AF: 0.0101 AC: 1543 AN: 152346 Hom.: 21 Cov.: 34 AF XY: 0.00929 AC XY: 692 AN XY: 74484

Gnomad4 AFR AF: 0.0347

Gnomad4 AMR AF: 0.00470

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00710

Alfa AF: 0.00282 Hom.: 0

Bravo AF: 0.0115

ESP6500AA AF: 0.0289 AC: 127

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00311 AC: 376

Asia WGS AF: 0.00144 AC: 6 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 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	0.094
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.55
DANN	Benign	0.24
DEOGEN2	Benign	0.17	T;T;.
Eigen	Benign	-0.88
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.091	N
LIST_S2	Benign	0.50	T;T;T
MetaRNN	Benign	0.0025	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.1	M;.;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.4	N;.;.
REVEL	Benign	0.022
Sift	Benign	0.28	T;.;.
Sift4G	Benign	0.35	T;T;T
Polyphen		0.23	B;.;.
Vest4		0.15
MVP		0.20
MPC		0.24
ClinPred		0.0040	T
GERP RS		-0.40
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.049
gMVP		0.16

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: rs34916016; hg19: chr16-88555502;