Genetic Variant NM_001145347.2:c.11C>A (chr19-43597119-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001145347.2(ZNF576):c.11C>A(p.Pro4Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,814 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZNF576
NM_001145347.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.143

Publications

0 publications found

Variant links:

Genes affected

ZNF576 (HGNC:28357): (zinc finger protein 576) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and 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]

ZNF576 links:

SRRM5 (HGNC:37248): (serine/arginine repetitive matrix 5)

SRRM5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03187248).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145347.2. 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
	ZNF576	NM_001145347.2	MANE Select	c.11C>A	p.Pro4Gln	missense	Exon 2 of 3	NP_001138819.1	Q9H609
	ZNF576	NM_024327.2		c.11C>A	p.Pro4Gln	missense	Exon 2 of 3	NP_077303.1	Q9H609

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF576	ENST00000336564.5	TSL:1 MANE Select	c.11C>A	p.Pro4Gln	missense	Exon 2 of 3	ENSP00000337852.4	Q9H609
ZNF576	ENST00000391965.6	TSL:2	c.11C>A	p.Pro4Gln	missense	Exon 2 of 3	ENSP00000375827.2	Q9H609
ZNF576	ENST00000525771.1	TSL:2	c.11C>A	p.Pro4Gln	missense	Exon 1 of 2	ENSP00000436182.1	Q9H609

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251424

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461814

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727206

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.0000224

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:

86244

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111970

Other (OTH)

AF:

0.00

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

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

0.069

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.77

CADD

Benign

8.4

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.0059

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.048

LIST_S2

Benign

0.38

M_CAP

Benign

0.0022

MetaRNN

Benign

0.032

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.81

PhyloP100

-0.14

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.34

REVEL

Benign

0.070

Sift

Benign

0.32

Sift4G

Uncertain

0.059

Polyphen

0.0030

Vest4

0.19

MutPred

0.23

Loss of sheet (P = 0.0483)

MVP

0.22

MPC

0.62

ClinPred

0.044

GERP RS

-1.9

Varity_R

0.027

gMVP

0.28

Mutation Taster

=299/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over