Genetic Variant ZNF441:p.Gln89Gln (chr19-11780091-A-G) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_152355.3(ZNF441):c.267A>G(p.Gln89Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00153 in 1,614,188 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0079 ( 15 hom., cov: 32)

Exomes 𝑓: 0.00087 ( 19 hom. )

Consequence

ZNF441
NM_152355.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0790

Publications

2 publications found

Variant links:

Genes affected

ZNF441 (HGNC:20875): (zinc finger protein 441) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF441 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 19-11780091-A-G is Benign according to our data. Variant chr19-11780091-A-G is described in ClinVar as Benign. ClinVar VariationId is 784386.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.079 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00791 (1205/152324) while in subpopulation AFR AF = 0.0279 (1161/41574). AF 95% confidence interval is 0.0266. There are 15 homozygotes in GnomAd4. There are 592 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 15 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152355.3. 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
	ZNF441	NM_152355.3	MANE Select	c.267A>G	p.Gln89Gln	synonymous	Exon 4 of 4	NP_689568.2	Q8N8Z8-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF441	ENST00000357901.5	TSL:3 MANE Select	c.267A>G	p.Gln89Gln	synonymous	Exon 4 of 4	ENSP00000350576.4	Q8N8Z8-1
ZNF441	ENST00000409902.5	TSL:2	n.*196A>G		non_coding_transcript_exon	Exon 5 of 5	ENSP00000386658.2	A0A0A0MSF7
ZNF441	ENST00000409902.5	TSL:2	n.*196A>G		3_prime_UTR	Exon 5 of 5	ENSP00000386658.2	A0A0A0MSF7

Frequencies

GnomAD3 genomes

AF:

0.00793

AC:

1207

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0281

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00214

AC:

539

AN:

251464

AF XY:

0.00171

show subpopulations

Gnomad AFR exome

AF:

0.0303

Gnomad AMR exome

AF:

0.000867

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000967

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.000865

AC:

1265

AN:

1461864

Hom.:

Cov.:

AF XY:

0.000732

AC XY:

532

AN XY:

727232

show subpopulations

African (AFR)

AF:

0.0296

AC:

990

AN:

33480

American (AMR)

AF:

0.000894

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00329

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000746

AC:

AN:

1111992

Other (OTH)

AF:

0.00220

AC:

133

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

153

229

306

382

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<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:

0.00791

AC:

1205

AN:

152324

Hom.:

Cov.:

AF XY:

0.00795

AC XY:

592

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.0279

AC:

1161

AN:

41574

American (AMR)

AF:

0.00190

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68024

Other (OTH)

AF:

0.00284

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

116

174

232

290

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00418

Hom.:

Bravo

AF:

0.00872

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.66

(source)

DANN

Benign

0.29

PhyloP100

0.079

Mutation Taster

=100/0

polymorphism

(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