Genetic Variant ZNF875:p.Thr30Met (chr19-37344773-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_181786.4(ZNF875):c.89C>T(p.Thr30Met) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000138 in 1,381,664 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

ZNF875
NM_181786.4 missense, splice_region

Scores

Splicing: ADA: 0.00004682

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.605

Publications

0 publications found

Variant links:

Genes affected

ZNF875 (HGNC:4928): (zinc finger protein 875) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific 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]

ZNF875 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0819256).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181786.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF875	NM_001353803.2	MANE Select	c.34-2417C>T		intron	N/A	NP_001340732.1	P10072-2
ZNF875	NM_181786.4		c.89C>T	p.Thr30Met	missense splice_region	Exon 3 of 6	NP_861451.1	P10072-1
ZNF875	NM_001329761.2		c.34-2417C>T		intron	N/A	NP_001316690.1	K7EPW3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF875	ENST00000324411.8	TSL:1	c.89C>T	p.Thr30Met	missense splice_region	Exon 3 of 6	ENSP00000315505.3	P10072-1
ZNF875	ENST00000392153.8	TSL:1 MANE Select	c.34-2417C>T		intron	N/A	ENSP00000375994.3	P10072-2
ZNF875	ENST00000591259.5	TSL:1	c.34-2417C>T		intron	N/A	ENSP00000466472.1	K7EME6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000159

AC:

AN:

251410

AF XY:

0.0000147

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000138

AC:

AN:

1381664

Hom.:

Cov.:

AF XY:

0.0000173

AC XY:

AN XY:

692122

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31566

American (AMR)

AF:

0.0000224

AC:

AN:

44616

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25654

East Asian (EAS)

AF:

0.00

AC:

AN:

39312

South Asian (SAS)

AF:

0.0000118

AC:

AN:

84638

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53370

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5610

European-Non Finnish (NFE)

AF:

0.0000164

AC:

AN:

1039228

Other (OTH)

AF:

0.00

AC:

AN:

57670

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

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

Cov.:

Alfa

AF:

0.0000579

Hom.:

Bravo

AF:

0.0000113

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.74

CADD

Benign

3.7

(source)

DANN

Benign

0.70

DEOGEN2

Benign

0.018

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0039

LIST_S2

Benign

0.32

M_CAP

Benign

0.0018

MetaRNN

Benign

0.082

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.0

PhyloP100

-0.60

PrimateAI

Benign

0.40

PROVEAN

Benign

0.62

REVEL

Benign

0.034

Sift

Benign

0.14

Sift4G

Benign

0.088

Polyphen

0.59

Vest4

0.049

MVP

0.048

MPC

0.037

ClinPred

0.031

GERP RS

0.12

Varity_R

0.014

gMVP

0.068

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000047

SpliceAI score (max)

0.17

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over