19-43607823-G-T

Position:

• chr19-43607823-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_182498.4(ZNF428):​c.361C>A​(p.Gln121Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF428 NM_182498.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.45

Genes affected

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

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

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22534454).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF428	NM_182498.4	c.361C>A	p.Gln121Lys	missense_variant	3/3	ENST00000300811.8	NP_872304.2
ZNF428	XM_047438168.1	c.361C>A	p.Gln121Lys	missense_variant	4/4		XP_047294124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF428	ENST00000300811.8	c.361C>A	p.Gln121Lys	missense_variant	3/3	1	NM_182498.4	ENSP00000300811	P1
ZNF428	ENST00000598676.1	c.460C>A	p.Gln154Lys	missense_variant	4/4	5		ENSP00000469484
SRRM5	ENST00000607544.1	c.-95-4204G>T		intron_variant		2		ENSP00000476253	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1414350 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 699324

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

New York Genome Center

Mar 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.087	T;T
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.75	T;T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N;.
MutationTaster	Benign	0.99	N;D
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-2.4	N;.
REVEL	Benign	0.086
Sift	Uncertain	0.024	D;.
Sift4G	Benign	0.73	T;.
Polyphen		0.86	P;.
Vest4		0.39
MutPred		0.31		Gain of methylation at Q121 (P = 0.0043);.;
MVP		0.12
MPC		1.2
ClinPred		0.66	D
GERP RS		4.5
Varity_R		0.22
gMVP		0.67

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

Other links and lift over

dbSNP: rs992390730; hg19: chr19-44111975;