11-65571396-A-C

Position:

• chr11-65571396-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006396.3(ZNRD2):​c.262A>C​(p.Asn88His) 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: 7.10

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3682099).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNRD2	NM_006396.3	c.262A>C	p.Asn88His	missense_variant	4/4	ENST00000309328.8	NP_006387.1
ZNRD2	NM_001303024.2	c.151A>C	p.Asn51His	missense_variant	3/3		NP_001289953.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNRD2	ENST00000309328.8	c.262A>C	p.Asn88His	missense_variant	4/4	1	NM_006396.3	ENSP00000312318	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 21, 2023

The c.262A>C (p.N88H) alteration is located in exon 4 (coding exon 4) of the SSSCA1 gene. This alteration results from a A to C substitution at nucleotide position 262, causing the asparagine (N) at amino acid position 88 to be replaced by a histidine (H). 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	Pathogenic	0.76
BayesDel_addAF	Benign	-0.044	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	24
DANN	Benign	0.83
DEOGEN2	Benign	0.12	T;T;T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.86	D;D;D
MetaRNN	Benign	0.37	T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.9	L;.;.
MutationTaster	Benign	1.0	D;D;D;N
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-2.2	N;N;N
REVEL	Benign	0.17
Sift	Uncertain	0.0090	D;D;D
Sift4G	Uncertain	0.019	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.51
MutPred		0.28		Loss of solvent accessibility (P = 0.2668);.;.;
MVP		0.86
MPC		0.50
ClinPred		0.88	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.30
gMVP		0.51

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: chr11-65338867;