chr19-44010600-G-T

Variant names:

• chr19-44010600-G-T
• rs1599852904
• NM_006300.4:c.561G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006300.4(ZNF230):​c.561G>T​(p.Gln187His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF230 NM_006300.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.116
• Publications: 0 publications found

Genes affected

ZNF230 (HGNC:13024): (zinc finger protein 230) 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]

ENSG00000293690 (HGNC:):

ACMG classification

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=0.21725431).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF230	NM_006300.4	c.561G>T	p.Gln187His	missense_variant	Exon 5 of 5	ENST00000429154.7	NP_006291.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF230	ENST00000429154.7	c.561G>T	p.Gln187His	missense_variant	Exon 5 of 5	1	NM_006300.4	ENSP00000409318.1
ZNF230	ENST00000585568.5	n.*471G>T		non_coding_transcript_exon_variant	Exon 5 of 5	5		ENSP00000465324.1
ZNF230	ENST00000585568.5	n.*471G>T		3_prime_UTR_variant	Exon 5 of 5	5		ENSP00000465324.1
ENSG00000293690	ENST00000718359.1	n.249-11368C>A		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 22, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.561G>T (p.Q187H) alteration is located in exon 5 (coding exon 4) of the ZNF230 gene. This alteration results from a G to T substitution at nucleotide position 561, causing the glutamine (Q) at amino acid position 187 to be replaced by a histidine (H). 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	Uncertain	0.41
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.052	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.0018	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.8	L
PhyloP100		-0.12
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.12
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.97	D
Vest4		0.15
MutPred		0.54		Loss of MoRF binding (P = 0.0984);
MVP		0.32
MPC		0.55
ClinPred		0.94	D
GERP RS		0.13
Varity_R		0.31
gMVP		0.022
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs1599852904; hg19: chr19-44514752;