dbSNP rs9304994: ZNF257:c.*499G>A (chr19-22089941-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_033468.4(ZNF257):c.*499G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.661 in 156,190 control chromosomes in the GnomAD database, including 34,872 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.66 ( 33973 hom., cov: 33)

Exomes 𝑓: 0.64 ( 899 hom. )

Consequence

ZNF257
NM_033468.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.187

Publications

11 publications found

Variant links:

Genes affected

ZNF257 (HGNC:13498): (zinc finger protein 257) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF257 links:

ENSG00000308832 (HGNC:):

ENSG00000308832 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.817 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033468.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZNF257	NM_033468.4	MANE Select	c.*499G>A	3_prime_UTR	Exon 4 of 4	NP_258429.2	Q9Y2Q1-1
ZNF257	NM_001316996.2		c.*499G>A	3_prime_UTR	Exon 5 of 5	NP_001303925.1	Q9Y2Q1-3
ZNF257	NM_001316997.2		c.*499G>A	3_prime_UTR	Exon 5 of 5	NP_001303926.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZNF257	ENST00000594947.6	TSL:4 MANE Select	c.*499G>A	3_prime_UTR	Exon 4 of 4	ENSP00000470209.1	Q9Y2Q1-1
ZNF257	ENST00000435820.6	TSL:1	n.*2204G>A	non_coding_transcript_exon	Exon 5 of 5	ENSP00000406147.2	M0R321
ZNF257	ENST00000435820.6	TSL:1	n.*2204G>A	3_prime_UTR	Exon 5 of 5	ENSP00000406147.2	M0R321

Frequencies

GnomAD3 genomes

AF:

0.661

AC:

100398

AN:

151782

Hom.:

33927

Cov.:

show subpopulations

Gnomad AFR

AF:

0.796

Gnomad AMI

AF:

0.470

Gnomad AMR

AF:

0.647

Gnomad ASJ

AF:

0.707

Gnomad EAS

AF:

0.681

Gnomad SAS

AF:

0.839

Gnomad FIN

AF:

0.571

Gnomad MID

AF:

0.655

Gnomad NFE

AF:

0.583

Gnomad OTH

AF:

0.651

GnomAD4 exome

AF:

0.641

AC:

2750

AN:

4290

Hom.:

899

Cov.:

AF XY:

0.641

AC XY:

1458

AN XY:

2274

show subpopulations

African (AFR)

AF:

0.900

AC:

AN:

American (AMR)

AF:

0.658

AC:

603

AN:

916

Ashkenazi Jewish (ASJ)

AF:

0.636

AC:

AN:

East Asian (EAS)

AF:

0.619

AC:

AN:

South Asian (SAS)

AF:

0.861

AC:

463

AN:

538

European-Finnish (FIN)

AF:

0.660

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.590

AC:

1496

AN:

2536

Other (OTH)

AF:

0.597

AC:

AN:

134

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

133

177

221

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

152

190

<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:

0.662

AC:

100504

AN:

151900

Hom.:

33973

Cov.:

AF XY:

0.667

AC XY:

49492

AN XY:

74216

show subpopulations

African (AFR)

AF:

0.796

AC:

33003

AN:

41478

American (AMR)

AF:

0.647

AC:

9865

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.707

AC:

2451

AN:

3468

East Asian (EAS)

AF:

0.681

AC:

3528

AN:

5180

South Asian (SAS)

AF:

0.839

AC:

4049

AN:

4826

European-Finnish (FIN)

AF:

0.571

AC:

5996

AN:

10494

Middle Eastern (MID)

AF:

0.663

AC:

195

AN:

294

European-Non Finnish (NFE)

AF:

0.584

AC:

39610

AN:

67882

Other (OTH)

AF:

0.654

AC:

1379

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1699

3398

5098

6797

8496

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

798

1596

2394

3192

3990

<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:

0.623

Hom.:

42484

Bravo

AF:

0.665

Asia WGS

AF:

0.782

AC:

2702

AN:

3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.1

(source)

DANN

Benign

0.16

PhyloP100

-0.19

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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