11-65571504-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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]

ZNRD2-DT (HGNC:27384): (ZNRD2 divergent transcript)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24445346).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006396.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNRD2	NM_006396.3	MANE Select	c.370C>T	p.His124Tyr	missense	Exon 4 of 4	NP_006387.1	O60232
	ZNRD2	NM_001303024.2		c.259C>T	p.His87Tyr	missense	Exon 3 of 3	NP_001289953.1	G3V1B8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNRD2	ENST00000309328.8	TSL:1 MANE Select	c.370C>T	p.His124Tyr	missense	Exon 4 of 4	ENSP00000312318.3	O60232
	ZNRD2	ENST00000913762.1		c.376C>T	p.His126Tyr	missense	Exon 4 of 4	ENSP00000583821.1
	ZNRD2	ENST00000533115.5	TSL:3	c.352C>T	p.His118Tyr	missense	Exon 3 of 4	ENSP00000435432.1	H0YEB6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	0.055
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		4.7
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.78	N
REVEL	Benign	0.12
Sift	Benign	0.14	T
Sift4G	Benign	0.34	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
Mutation Taster		=69/31	polymorphism

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

Other links and lift over

hg19: chr11-65338975;