16-88489094-G-C

Variant names:

• chr16-88489094-G-C
• rs34916016
• NM_153813.3:c.209G>C

Variant summary

Our verdict is Benign. The variant received -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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• 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
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• congenital heart disease

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 21 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153813.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFPM1	NM_153813.3	MANE Select	c.209G>C	p.Gly70Ala	missense	Exon 3 of 10	NP_722520.2	Q8IX07

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFPM1	ENST00000319555.8	TSL:1 MANE Select	c.209G>C	p.Gly70Ala	missense	Exon 3 of 10	ENSP00000326630.2	Q8IX07
	ZFPM1	ENST00000569086.5	TSL:2	c.209G>C	p.Gly70Ala	missense	Exon 3 of 6	ENSP00000482796.1	A0A087WZP1
	ZFPM1	ENST00000562437.2	TSL:2	c.209G>C	p.Gly70Ala	missense	Exon 3 of 5	ENSP00000480412.1	A0A087WWQ0

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

GnomAD2 exomes AF: 0.00257 AC: 638 AN: 247902 AF XY: 0.00193

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 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

African (AFR) AF: 0.0369 AC: 1233 AN: 33454

American (AMR) AF: 0.00157 AC: 70 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.000104 AC: 9 AN: 86208

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52662

Middle Eastern (MID) AF: 0.00243 AC: 14 AN: 5762

European-Non Finnish (NFE) AF: 0.0000378 AC: 42 AN: 1111754

Other (OTH) AF: 0.00288 AC: 174 AN: 60346

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

African (AFR) AF: 0.0347 AC: 1444 AN: 41584

American (AMR) AF: 0.00470 AC: 72 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68026

Other (OTH) AF: 0.00710 AC: 15 AN: 2114

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.88
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.091	N
LIST_S2	Benign	0.50	T
MetaRNN	Benign	0.0025	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-0.68
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.022
Sift	Benign	0.28	T
Sift4G	Benign	0.35	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
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs34916016; hg19: chr16-88555502;