chr11-116782948-C-T

Variant names:

• chr11-116782948-C-T
• NM_003904.5:c.1063G>A

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_003904.5(ZPR1):​c.1063G>A​(p.Glu355Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZPR1 NM_003904.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.54
• Publications: 0 publications found

Genes affected

ZPR1 (HGNC:13051): (ZPR1 zinc finger) The protein encoded by this gene is found in the cytoplasm of quiescent cells but translocates to the nucleolus in proliferating cells. The encoded protein interacts with survival motor neuron protein (SMN1) to enhance pre-mRNA splicing and to induce neuronal differentiation and axonal growth. Defects in this gene or the SMN1 gene can cause spinal muscular atrophy. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2015]

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.97

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003904.5. 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
	ZPR1	NM_003904.5	MANE Select	c.1063G>A	p.Glu355Lys	missense	Exon 11 of 14	NP_003895.1	O75312
	ZPR1	NM_001317086.2		c.901G>A	p.Glu301Lys	missense	Exon 10 of 13	NP_001304015.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZPR1	ENST00000227322.8	TSL:1 MANE Select	c.1063G>A	p.Glu355Lys	missense	Exon 11 of 14	ENSP00000227322.3	O75312
	ZPR1	ENST00000900046.1		c.1093G>A	p.Glu365Lys	missense	Exon 11 of 14	ENSP00000570105.1
	ZPR1	ENST00000900049.1		c.1069G>A	p.Glu357Lys	missense	Exon 11 of 14	ENSP00000570108.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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	Pathogenic	0.85
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.28
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.56	D
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.91	D
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.97	D
MetaSVM	Uncertain	0.40	D
MutationAssessor	Pathogenic	4.0	H
PhyloP100		7.5
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-3.9	D
REVEL	Uncertain	0.53
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.012	D
Polyphen		0.82	P
Vest4		0.97
MutPred		0.87		Gain of solvent accessibility (P = 0.012)
MVP		0.75
MPC		0.74
ClinPred		1.0	D
GERP RS		6.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.70
gMVP		0.95
Mutation Taster		=14/86	disease causing

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: chr11-116653664;