rs546662515

Variant names:

• chr20-41202188-G-A
• NM_001384317.1:c.2729C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-41202188-G-A
• chr20-41202188-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001384317.1(ZHX3):​c.2729C>T​(p.Thr910Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ZHX3 NM_001384317.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.957

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 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=0.06528643).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZHX3	NM_001384317.1	c.2729C>T	p.Thr910Ile	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.2729C>T	p.Thr910Ile	missense_variant	Exon 3 of 4		NM_001384317.1	ENSP00000506788.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461890 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727246

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: 0.00000180

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	11
DANN	Uncertain	0.98
DEOGEN2	Benign	0.014	T;T;T;T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.70	.;.;.;T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.065	T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.69	N;N;N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.92	.;N;N;.
REVEL	Benign	0.070
Sift	Benign	0.17	.;T;T;.
Sift4G	Benign	0.25	T;T;T;T
Polyphen		0.0090	B;B;B;B
Vest4		0.066
MutPred		0.23		Loss of phosphorylation at T910 (P = 0.0238);Loss of phosphorylation at T910 (P = 0.0238);Loss of phosphorylation at T910 (P = 0.0238);Loss of phosphorylation at T910 (P = 0.0238);
MVP		0.23
MPC		0.25
ClinPred		0.053	T
GERP RS		3.0
Varity_R		0.029
gMVP		0.067

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-39830828;