rs1555344723
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5
The NM_033400.3(ZFHX2):c.5738G>A(p.Arg1913Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000217 in 1,384,164 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000022 ( 0 hom. )
Consequence
ZFHX2
NM_033400.3 missense
NM_033400.3 missense
Scores
5
11
3
Clinical Significance
Conservation
PhyloP100: 7.85
Genes affected
ZFHX2 (HGNC:20152): (zinc finger homeobox 2) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in regulation of sensory perception of pain. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]
ZFHX2-AS1 (HGNC:52658): (ZFHX2 antisense RNA 1)
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 14-23524204-C-T is Pathogenic according to our data. Variant chr14-23524204-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 487556.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ZFHX2 | NM_033400.3 | c.5738G>A | p.Arg1913Lys | missense_variant | 9/10 | ENST00000419474.5 | NP_207646.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ZFHX2 | ENST00000419474.5 | c.5738G>A | p.Arg1913Lys | missense_variant | 9/10 | 5 | NM_033400.3 | ENSP00000413418 | P1 | |
ZFHX2-AS1 | ENST00000553985.1 | n.238+9788C>T | intron_variant, non_coding_transcript_variant | 2 | ||||||
ZFHX2-AS1 | ENST00000554403.1 | n.1068+9788C>T | intron_variant, non_coding_transcript_variant | 2 | ||||||
ZFHX2-AS1 | ENST00000556354.5 | n.465+9788C>T | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000217 AC: 3AN: 1384164Hom.: 0 Cov.: 40 AF XY: 0.00000146 AC XY: 1AN XY: 683020
GnomAD4 exome
AF:
AC:
3
AN:
1384164
Hom.:
Cov.:
40
AF XY:
AC XY:
1
AN XY:
683020
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Indifference to pain, congenital, autosomal dominant Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 31, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Uncertain
T
MetaSVM
Uncertain
D
MutationAssessor
Benign
N
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Benign
T
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Gain of catalytic residue at R1918 (P = 0.0075);
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at