11-65571504-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006396.3(ZNRD2):​c.370C>T​(p.His124Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

ZNRD2
NM_006396.3 missense

Scores

1
4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.75
Variant links:
Genes affected
ZNRD2 (HGNC:11328): (zinc ribbon domain containing 2) This antigen is recognized by a subset of anti-centromere antibodies from patients with scleroderma and/or Sjogren's syndrome. Subcellular localization has not yet been established. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

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=0.24445346).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNRD2NM_006396.3 linkc.370C>T p.His124Tyr missense_variant Exon 4 of 4 ENST00000309328.8 NP_006387.1 O60232
ZNRD2NM_001303024.2 linkc.259C>T p.His87Tyr missense_variant Exon 3 of 3 NP_001289953.1 G3V1B8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNRD2ENST00000309328.8 linkc.370C>T p.His124Tyr missense_variant Exon 4 of 4 1 NM_006396.3 ENSP00000312318.3 O60232

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Apr 12, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.370C>T (p.H124Y) alteration is located in exon 4 (coding exon 4) of the SSSCA1 gene. This alteration results from a C to T substitution at nucleotide position 370, causing the histidine (H) at amino acid position 124 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.47
BayesDel_addAF
Benign
-0.049
T
BayesDel_noAF
Benign
-0.31
CADD
Benign
23
DANN
Uncertain
0.98
DEOGEN2
Benign
0.079
T;T;T
Eigen
Benign
0.055
Eigen_PC
Benign
0.19
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.88
D;D;D
M_CAP
Benign
0.0042
T
MetaRNN
Benign
0.24
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.8
L;.;.
PrimateAI
Pathogenic
0.82
D
PROVEAN
Benign
-0.78
N;N;N
REVEL
Benign
0.12
Sift
Benign
0.14
T;T;T
Sift4G
Benign
0.34
T;T;T
Polyphen
0.44
B;.;.
Vest4
0.40
MutPred
0.24
Gain of phosphorylation at H124 (P = 0.0172);.;.;
MVP
0.79
MPC
0.37
ClinPred
0.67
D
GERP RS
4.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.8
Varity_R
0.16
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-65338975; API