Genetic Variant ZNF75A:c.-117+1191T>C (chr16-3306834-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000669516.2(ZNF75A):c.-117+1191T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 152,012 control chromosomes in the GnomAD database, including 21,225 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 0.50 ( 21224 hom., cov: 32)

Exomes 𝑓: 0.28 ( 1 hom. )

Consequence

ZNF75A
ENST00000669516.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0550

Publications

10 publications found

Variant links:

Genes affected

ZNF75A (HGNC:13146): (zinc finger protein 75A) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF75A links:

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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=-0.97).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000669516.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ZNF75A	NM_001302109.2	MANE Select	c.-117+1191T>C	intron	N/A	NP_001289038.1
ZNF75A	NM_001324041.1		c.-117+428T>C	intron	N/A	NP_001310970.1
ZNF75A	NM_153028.4		c.-316+1191T>C	intron	N/A	NP_694573.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ZNF75A	ENST00000669516.2	MANE Select	c.-117+1191T>C	intron	N/A	ENSP00000499415.1
ZNF75A	ENST00000575234.1	TSL:6	n.1351T>C	non_coding_transcript_exon	Exon 1 of 1
ZNF75A	ENST00000574298.6	TSL:2	c.-316+1191T>C	intron	N/A	ENSP00000459566.1

Frequencies

GnomAD3 genomes

AF:

0.505

AC:

76630

AN:

151876

Hom.:

21184

Cov.:

show subpopulations

Gnomad AFR

AF:

0.712

Gnomad AMI

AF:

0.408

Gnomad AMR

AF:

0.507

Gnomad ASJ

AF:

0.384

Gnomad EAS

AF:

0.0918

Gnomad SAS

AF:

0.156

Gnomad FIN

AF:

0.446

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.453

Gnomad OTH

AF:

0.478

GnomAD4 exome

AF:

0.278

AC:

AN:

Hom.:

Cov.:

AF XY:

0.333

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.250

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

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:

0.505

AC:

76730

AN:

151994

Hom.:

21224

Cov.:

AF XY:

0.496

AC XY:

36861

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.712

AC:

29494

AN:

41412

American (AMR)

AF:

0.507

AC:

7739

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.384

AC:

1332

AN:

3472

East Asian (EAS)

AF:

0.0920

AC:

477

AN:

5184

South Asian (SAS)

AF:

0.156

AC:

750

AN:

4818

European-Finnish (FIN)

AF:

0.446

AC:

4712

AN:

10558

Middle Eastern (MID)

AF:

0.296

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.453

AC:

30767

AN:

67966

Other (OTH)

AF:

0.476

AC:

1001

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1750

3500

5251

7001

8751

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

632

1264

1896

2528

3160

<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:

0.464

Hom.:

7581

Bravo

AF:

0.523

Asia WGS

AF:

0.199

AC:

695

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

4.0

(source)

DANN

Benign

0.78

PhyloP100

-0.055

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