11-65571712-G-A

Variant names:

• chr11-65571712-G-A
• rs764039631
• NM_006396.3:c.578G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006396.3(ZNRD2):​c.578G>A​(p.Ser193Asn) 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. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S193I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNRD2 NM_006396.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.95
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31368184).

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.578G>A	p.Ser193Asn	missense	Exon 4 of 4	NP_006387.1	O60232
	ZNRD2	NM_001303024.2		c.467G>A	p.Ser156Asn	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.578G>A	p.Ser193Asn	missense	Exon 4 of 4	ENSP00000312318.3	O60232
	ZNRD2	ENST00000913762.1		c.584G>A	p.Ser195Asn	missense	Exon 4 of 4	ENSP00000583821.1
	ZNRD2	ENST00000533115.5	TSL:3	c.560G>A	p.Ser187Asn	missense	Exon 3 of 4	ENSP00000435432.1	H0YEB6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.091	T
Eigen	Benign	0.097
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.3	L
PhyloP100		5.0
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.046
Sift	Uncertain	0.025	D
Sift4G	Uncertain	0.056	T
Polyphen		0.28	B
Vest4		0.34
MutPred		0.32		Loss of disorder (P = 0.0467)
MVP		0.86
MPC		0.23
ClinPred		0.87	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.18
gMVP		0.54
Mutation Taster		=86/14	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

dbSNP: rs764039631; hg19: chr11-65339183;