20-41202259-T-G

Variant names:

• chr20-41202259-T-G
• rs34229622
• NM_001384317.1:c.2658A>C

Variant summary

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

The NM_001384317.1(ZHX3):​c.2658A>C​(p.Lys886Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: ZHX3 NM_001384317.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.891

Genes affected

ZHX3 (HGNC:15935): (zinc fingers and homeoboxes 3) This gene encodes a member of the zinc fingers and homeoboxes (ZHX) gene family. The encoded protein contains two C2H2-type zinc fingers and five homeodomains and forms a dimer with itself or with zinc fingers and homeoboxes family member 1. In the nucleus, the dimerized protein interacts with the A subunit of the ubiquitous transcription factor nuclear factor-Y and may function as a transcriptional repressor. [provided by RefSeq, Jul 2008]

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=0.08969647).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZHX3	NM_001384317.1	c.2658A>C	p.Lys886Asn	missense_variant	Exon 3 of 4	ENST00000683867.1	NP_001371246.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZHX3	ENST00000683867.1	c.2658A>C	p.Lys886Asn	missense_variant	Exon 3 of 4		NM_001384317.1	ENSP00000506788.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000821 AC: 12 AN: 1461878 Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7 AN XY: 727240

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: 0.0000108

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	11
DANN	Uncertain	1.0
DEOGEN2	Benign	0.022	T;T;T;T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.81	.;.;.;T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.090	T;T;T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.3	M;M;M;M
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.4	.;N;N;.
REVEL	Benign	0.057
Sift	Uncertain	0.0080	.;D;D;.
Sift4G	Benign	0.12	T;T;T;T
Polyphen		0.41	B;B;B;B
Vest4		0.39
MutPred		0.37		Loss of ubiquitination at K886 (P = 0.0067);Loss of ubiquitination at K886 (P = 0.0067);Loss of ubiquitination at K886 (P = 0.0067);Loss of ubiquitination at K886 (P = 0.0067);
MVP		0.21
MPC		0.81
ClinPred		0.86	D
GERP RS		-3.9
Varity_R		0.20
gMVP		0.43

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: rs34229622; hg19: chr20-39830899;