dbSNP rs1543922: ZNF175:c.199+66C>T (chr19-51581583-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_007147.4(ZNF175):c.199+66C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0331 in 1,570,738 control chromosomes in the GnomAD database, including 4,967 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 0.11 ( 2209 hom., cov: 32)

Exomes 𝑓: 0.025 ( 2758 hom. )

Consequence

ZNF175
NM_007147.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0550

Publications

9 publications found

Variant links:

Genes affected

ZNF175 (HGNC:12964): (zinc finger protein 175) Enables DNA-binding transcription activator activity, RNA polymerase II-specific; DNA-binding transcription repressor activity, RNA polymerase II-specific; and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II and positive regulation of transcription by RNA polymerase II. Located in cytosol; intermediate filament cytoskeleton; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZNF175 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=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007147.4. 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
	ZNF175	NM_007147.4	MANE Select	c.199+66C>T		intron	N/A	NP_009078.1	Q9Y473

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZNF175	ENST00000262259.7	TSL:1 MANE Select	c.199+66C>T	intron	N/A	ENSP00000262259.2	Q9Y473
ZNF175	ENST00000958253.1		c.199+66C>T	intron	N/A	ENSP00000628312.1
ZNF175	ENST00000912771.1		c.199+66C>T	intron	N/A	ENSP00000582830.1

Frequencies

GnomAD3 genomes

AF:

0.109

AC:

16599

AN:

152044

Hom.:

2207

Cov.:

show subpopulations

Gnomad AFR

AF:

0.315

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0956

Gnomad ASJ

AF:

0.00865

Gnomad EAS

AF:

0.141

Gnomad SAS

AF:

0.0296

Gnomad FIN

AF:

0.0419

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.00866

Gnomad OTH

AF:

0.0877

GnomAD4 exome

AF:

0.0249

AC:

35379

AN:

1418576

Hom.:

2758

Cov.:

AF XY:

0.0235

AC XY:

16443

AN XY:

700462

show subpopulations

African (AFR)

AF:

0.330

AC:

10721

AN:

32442

American (AMR)

AF:

0.0924

AC:

3705

AN:

40112

Ashkenazi Jewish (ASJ)

AF:

0.00976

AC:

223

AN:

22848

East Asian (EAS)

AF:

0.148

AC:

5800

AN:

39296

South Asian (SAS)

AF:

0.0247

AC:

1947

AN:

78872

European-Finnish (FIN)

AF:

0.0375

AC:

1941

AN:

51734

Middle Eastern (MID)

AF:

0.0360

AC:

199

AN:

5534

European-Non Finnish (NFE)

AF:

0.00753

AC:

8202

AN:

1089266

Other (OTH)

AF:

0.0452

AC:

2641

AN:

58472

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

1695

3390

5086

6781

8476

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

610

1220

1830

2440

3050

<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:

0.109

AC:

16622

AN:

152162

Hom.:

2209

Cov.:

AF XY:

0.110

AC XY:

8155

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.314

AC:

13023

AN:

41450

American (AMR)

AF:

0.0956

AC:

1463

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00865

AC:

AN:

3470

East Asian (EAS)

AF:

0.141

AC:

732

AN:

5180

South Asian (SAS)

AF:

0.0292

AC:

141

AN:

4832

European-Finnish (FIN)

AF:

0.0419

AC:

444

AN:

10604

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00866

AC:

589

AN:

68014

Other (OTH)

AF:

0.0868

AC:

183

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

611

1222

1834

2445

3056

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

162

324

486

648

810

<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:

0.0436

Hom.:

2770

Bravo

AF:

0.122

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

3.3

(source)

DANN

Benign

0.64

PhyloP100

0.055

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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