dbSNP rs769825796: ZFPM1:p.Pro94Pro (chr16-88514400-G-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_153813.3(ZFPM1):c.282G>A(p.Pro94Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000352 in 1,564,648 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000037 ( 0 hom. )

Consequence

ZFPM1
NM_153813.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.28

Publications

1 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 16-88514400-G-A is Benign according to our data. Variant chr16-88514400-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2646974.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.28 with no splicing effect.

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.282G>A	p.Pro94Pro	synonymous	Exon 4 of 10	NP_722520.2	Q8IX07
	ZFPM1-AS1	NR_148997.1		n.390-1097C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZFPM1	ENST00000319555.8	TSL:1 MANE Select	c.282G>A	p.Pro94Pro	synonymous	Exon 4 of 10	ENSP00000326630.2	Q8IX07
ZFPM1	ENST00000569086.5	TSL:2	c.282G>A	p.Pro94Pro	synonymous	Exon 4 of 6	ENSP00000482796.1	A0A087WZP1
ZFPM1	ENST00000562437.2	TSL:2	c.282G>A	p.Pro94Pro	synonymous	Exon 4 of 5	ENSP00000480412.1	A0A087WWQ0

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000295

AC:

AN:

169716

AF XY:

0.0000110

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000767

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000593

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000368

AC:

AN:

1412406

Hom.:

Cov.:

AF XY:

0.0000286

AC XY:

AN XY:

698112

show subpopulations

African (AFR)

AF:

0.0000309

AC:

AN:

32394

American (AMR)

AF:

0.0000265

AC:

AN:

37794

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25282

East Asian (EAS)

AF:

0.0000270

AC:

AN:

37016

South Asian (SAS)

AF:

0.00

AC:

AN:

80284

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48266

Middle Eastern (MID)

AF:

0.000176

AC:

AN:

5694

European-Non Finnish (NFE)

AF:

0.0000405

AC:

AN:

1087170

Other (OTH)

AF:

0.0000684

AC:

AN:

58506

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152242

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41458

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5202

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000340

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

(source)

DANN

Benign

0.88

PhyloP100

1.3

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over