11-65571504-C-T

Variant names:

• chr11-65571504-C-T
• NM_006396.3:c.370C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.75

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]

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=0.24445346).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNRD2	NM_006396.3	c.370C>T	p.His124Tyr	missense_variant	Exon 4 of 4	ENST00000309328.8	NP_006387.1
ZNRD2	NM_001303024.2	c.259C>T	p.His87Tyr	missense_variant	Exon 3 of 3		NP_001289953.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNRD2	ENST00000309328.8	c.370C>T	p.His124Tyr	missense_variant	Exon 4 of 4	1	NM_006396.3	ENSP00000312318.3

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

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;