Genetic Variant ZNF181:p.Val107Asp (chr19-34740701-T-A) – 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_001029997.4(ZNF181):c.320T>A(p.Val107Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V107A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZNF181
NM_001029997.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.96

Publications

0 publications found

Variant links:

Genes affected

ZNF181 (HGNC:12971): (zinc finger protein 181) Zinc finger proteins have been shown to interact with nucleic acids and to have diverse functions. The zinc finger domain is a conserved amino acid sequence motif containing 2 specifically positioned cysteines and 2 histidines that are involved in coordinating zinc. Kruppel-related proteins form 1 family of zinc finger proteins. See MIM 604749 for additional information on zinc finger proteins.[supplied by OMIM, Jul 2003]

ZNF181 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=0.073292464).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001029997.4. 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
	ZNF181	NM_001029997.4	MANE Select	c.320T>A	p.Val107Asp	missense	Exon 4 of 4	NP_001025168.2	Q2M3W8-1
	ZNF181	NM_001145665.2		c.317T>A	p.Val106Asp	missense	Exon 4 of 4	NP_001139137.1	Q2M3W8-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF181	ENST00000492450.3	TSL:1 MANE Select	c.320T>A	p.Val107Asp	missense	Exon 4 of 4	ENSP00000420727.1	Q2M3W8-1
ZNF181	ENST00000459757.6	TSL:1	c.317T>A	p.Val106Asp	missense	Exon 4 of 4	ENSP00000419435.1	Q2M3W8-3
ZNF181	ENST00000392232.7	TSL:5	c.452T>A	p.Val151Asp	missense	Exon 6 of 6	ENSP00000376065.3	F8W889

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460666

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726600

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33406

American (AMR)

AF:

0.00

AC:

AN:

44548

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26090

East Asian (EAS)

AF:

0.00

AC:

AN:

39682

South Asian (SAS)

AF:

0.00

AC:

AN:

85942

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53372

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111506

Other (OTH)

AF:

0.00

AC:

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.036

(source)

DANN

Benign

0.56

DEOGEN2

Benign

0.096

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0059

LIST_S2

Benign

0.76

M_CAP

Benign

0.0014

MetaRNN

Benign

0.073

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

PhyloP100

-3.0

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.010

Sift

Benign

0.11

Sift4G

Benign

0.18

Polyphen

0.42

Vest4

0.19

MutPred

0.41

Gain of disorder (P = 0.0284)

MVP

0.12

MPC

0.39

ClinPred

0.060

GERP RS

-3.4

Varity_R

0.20

gMVP

0.21

Mutation Taster

=99/1

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

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