chr20-41202381-T-G

Variant names:

• chr20-41202381-T-G
• rs201097931
• NM_001384317.1:c.2536A>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.2536A>C​(p.Asn846His) 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. 15/21 in silico tools predict 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)
• Consequence: ZHX3 NM_001384317.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.136

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=0.12197158).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZHX3	NM_001384317.1	c.2536A>C	p.Asn846His	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.2536A>C	p.Asn846His	missense_variant	Exon 3 of 4		NM_001384317.1	ENSP00000506788.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	16
DANN	Benign	0.94
DEOGEN2	Benign	0.016	T;T;.;T;T;T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.68	.;.;T;T;.;T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.12	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;L;L;.;L;L
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.0	.;N;N;N;N;.
REVEL	Benign	0.032
Sift	Benign	0.17	.;T;T;D;T;.
Sift4G	Benign	0.094	T;T;T;D;T;T
Polyphen		0.020	B;B;.;.;B;B
Vest4		0.16
MutPred		0.35		Gain of catalytic residue at E848 (P = 0.1871);Gain of catalytic residue at E848 (P = 0.1871);Gain of catalytic residue at E848 (P = 0.1871);.;Gain of catalytic residue at E848 (P = 0.1871);Gain of catalytic residue at E848 (P = 0.1871);
MVP		0.24
MPC		0.26
ClinPred		0.046	T
GERP RS		3.6
Varity_R		0.070
gMVP		0.49

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: rs201097931; hg19: chr20-39831021;