rs1555344723

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

Scores

5
11
3

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 7.85
Variant links:
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)

Genome browser will be placed here

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
ZFHX2NM_033400.3 linkuse as main transcriptc.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
ZFHX2ENST00000419474.5 linkuse as main transcriptc.5738G>A p.Arg1913Lys missense_variant 9/105 NM_033400.3 ENSP00000413418 P1Q9C0A1-1
ZFHX2-AS1ENST00000553985.1 linkuse as main transcriptn.238+9788C>T intron_variant, non_coding_transcript_variant 2
ZFHX2-AS1ENST00000554403.1 linkuse as main transcriptn.1068+9788C>T intron_variant, non_coding_transcript_variant 2
ZFHX2-AS1ENST00000556354.5 linkuse as main transcriptn.465+9788C>T intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000217
AC:
3
AN:
1384164
Hom.:
0
Cov.:
40
AF XY:
0.00000146
AC XY:
1
AN XY:
683020
show subpopulations
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:
0.00000278
Gnomad4 OTH exome
AF:
0.00
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 providedliterature onlyOMIMJan 31, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.86
BayesDel_addAF
Pathogenic
0.20
D
BayesDel_noAF
Uncertain
0.040
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.57
D
Eigen
Uncertain
0.53
Eigen_PC
Uncertain
0.56
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.96
D
M_CAP
Uncertain
0.12
D
MetaRNN
Uncertain
0.44
T
MetaSVM
Uncertain
0.68
D
MutationAssessor
Benign
0.21
N
MutationTaster
Benign
0.97
D;D
PrimateAI
Pathogenic
0.87
D
PROVEAN
Uncertain
-2.8
D
REVEL
Uncertain
0.62
Sift
Benign
0.066
T
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.45
MutPred
0.50
Gain of catalytic residue at R1918 (P = 0.0075);
MVP
0.63
ClinPred
0.98
D
GERP RS
4.7
Varity_R
0.48
gMVP
0.83

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1555344723; hg19: chr14-23993413; API