Genetic Variant NM_001172773.2:c.52G>A (chr19-57397048-G-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_001172773.2(ZNF548):c.52G>A(p.Gly18Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000417 in 1,605,972 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000041 ( 0 hom. )

Consequence

ZNF548
NM_001172773.2 missense, splice_region

Scores

Splicing: ADA: 0.1313

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.410

Publications

0 publications found

Variant links:

Genes affected

ZNF548 (HGNC:26561): (zinc finger protein 548) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-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]

ZNF548 links:

ENSG00000269533 (HGNC:):

ENSG00000269533 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=0.09791723).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001172773.2. 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
	ZNF548	NM_001172773.2	MANE Select	c.52G>A	p.Gly18Ser	missense splice_region	Exon 3 of 4	NP_001166244.1	Q8NEK5-2
	ZNF548	NM_152909.4		c.16G>A	p.Gly6Ser	missense splice_region	Exon 2 of 3	NP_690873.2	Q8NEK5-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF548	ENST00000336128.12	TSL:2 MANE Select	c.52G>A	p.Gly18Ser	missense splice_region	Exon 3 of 4	ENSP00000337555.6	Q8NEK5-2
ZNF548	ENST00000366197.10	TSL:1	c.16G>A	p.Gly6Ser	missense splice_region	Exon 2 of 3	ENSP00000379482.3	Q8NEK5-1
ENSG00000269533	ENST00000596400.1	TSL:4	c.51+2825G>A		intron	N/A	ENSP00000472277.1	M0R233

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000205

AC:

AN:

244406

AF XY:

0.0000151

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000626

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000269

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000406

AC:

AN:

1453790

Hom.:

Cov.:

AF XY:

0.0000318

AC XY:

AN XY:

723522

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32888

American (AMR)

AF:

0.0000239

AC:

AN:

41852

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25574

East Asian (EAS)

AF:

0.00

AC:

AN:

39640

South Asian (SAS)

AF:

0.00

AC:

AN:

85508

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53268

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5714

European-Non Finnish (NFE)

AF:

0.0000514

AC:

AN:

1109370

Other (OTH)

AF:

0.0000167

AC:

AN:

59976

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

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:

0.0000526

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41430

American (AMR)

AF:

0.000262

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.531

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000549

EpiControl

AF:

0.00

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

-0.47

BayesDel_noAF

Benign

-0.73

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.016

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.042

M_CAP

Benign

0.0019

MetaRNN

Benign

0.098

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.2

PhyloP100

0.41

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.8

REVEL

Benign

0.079

Sift

Benign

0.15

Sift4G

Benign

0.12

Polyphen

0.018

Vest4

0.070

MutPred

0.51

Gain of glycosylation at G6 (P = 0.049)

MVP

0.32

MPC

0.15

ClinPred

0.042

GERP RS

0.36

Varity_R

0.051

gMVP

0.15

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.13

dbscSNV1_RF

Benign

0.37

SpliceAI score (max)

0.040

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over