Variant chr19-43612710-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000300811.8(ZNF428):c.76+1519G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000189 in 1,551,604 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

ZNF428
ENST00000300811.8 intron

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.175

Variant links:

Genes affected

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

SRRM5 links:

ZNF428 (HGNC:20804): (zinc finger protein 428) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ZNF428 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.041060746).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRRM5	NM_001145641.2 linkuse as main transcript	c.589C>T	p.Arg197Cys	missense_variant	1/1	ENST00000417606.3	NP_001139113.1	B3KS81Q4G0Z0
ZNF428	NM_182498.4 linkuse as main transcript	c.76+1519G>A		intron_variant		ENST00000300811.8	NP_872304.2	Q96B54I6L9C8
ZNF428	XM_047438168.1 linkuse as main transcript	c.76+1519G>A		intron_variant			XP_047294124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SRRM5	ENST00000417606.3 linkuse as main transcript	c.589C>T	p.Arg197Cys	missense_variant	1/1	6	NM_001145641.2	ENSP00000414512.1	B3KS81
ZNF428	ENST00000300811.8 linkuse as main transcript	c.76+1519G>A		intron_variant		1	NM_182498.4	ENSP00000300811.2	Q96B54
SRRM5	ENST00000607544.1 linkuse as main transcript	c.589C>T	p.Arg197Cys	missense_variant	3/3	2		ENSP00000476253.1	B3KS81
ZNF428	ENST00000598676.1 linkuse as main transcript	c.76+1519G>A		intron_variant		5		ENSP00000469484.1	M0QXZ5

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000156

AC:

AN:

153862

Hom.:

AF XY:

0.000196

AC XY:

AN XY:

81660

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000439

Gnomad FIN exome

AF:

0.000331

Gnomad NFE exome

AF:

0.000285

Gnomad OTH exome

AF:

0.000231

GnomAD4 exome

AF:

0.000197

AC:

275

AN:

1399312

Hom.:

Cov.:

AF XY:

0.000206

AC XY:

142

AN XY:

690168

show subpopulations

Gnomad4 AFR exome

AF:

0.0000316

Gnomad4 AMR exome

AF:

0.0000280

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.000447

Gnomad4 NFE exome

AF:

0.000215

Gnomad4 OTH exome

AF:

0.000138

GnomAD4 genome

AF:

0.000118

AC:

AN:

152292

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000149

Hom.:

Bravo

AF:

0.0000718

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000131

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 06, 2023

The c.589C>T (p.R197C) alteration is located in exon 1 (coding exon 1) of the SRRM5 gene. This alteration results from a C to T substitution at nucleotide position 589, causing the arginine (R) at amino acid position 197 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0039

T;T

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.58

.;T

M_CAP

Benign

0.0046

MetaRNN

Benign

0.041

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.22

PROVEAN

Benign

-1.1

.;N

REVEL

Benign

0.13

Sift

Uncertain

0.0060

.;D

Sift4G

Uncertain

0.054

T;T

Polyphen

0.95

P;P

Vest4

0.10

MutPred

0.27

Loss of MoRF binding (P = 0.0025);Loss of MoRF binding (P = 0.0025);

MVP

0.055

MPC

0.048

ClinPred

0.12

GERP RS

3.2

Varity_R

0.088

gMVP

0.036

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over