rs11823543

Positions:

• chr11-116778419-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003904.5(ZPR1):​c.*506C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,688 control chromosomes in the GnomAD database, including 1,121 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.11 (1121 hom., cov: 32)
  • Exomes 𝑓: 0.021 (0 hom.)
• Consequence: ZPR1 NM_003904.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.265

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZPR1	NM_003904.5	c.*506C>T		3_prime_UTR_variant	14/14	ENST00000227322.8	NP_003895.1
ZPR1	NM_001317086.2	c.*506C>T		3_prime_UTR_variant	13/13		NP_001304015.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZPR1	ENST00000227322	c.*506C>T		3_prime_UTR_variant	14/14	1	NM_003904.5	ENSP00000227322.3
ZPR1	ENST00000444935	c.*506C>T		3_prime_UTR_variant	13/13	5		ENSP00000390391.1
ZPR1	ENST00000429220.5	c.*506C>T		3_prime_UTR_variant	12/12	5		ENSP00000394495.1

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16076 AN: 152104 Hom.: 1118 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.0858

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0429

Gnomad FIN AF: 0.0537

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0670

Gnomad OTH AF: 0.111

GnomAD4 exome AF: 0.0215 AC: 10 AN: 466 Hom.: 0 Cov.: 0 AF XY: 0.0123 AC XY: 3 AN XY: 244

Gnomad4 AFR exome AF: 0.167

Gnomad4 AMR exome AF: 0.0400

Gnomad4 ASJ exome AF: 0.125

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.100

Gnomad4 NFE exome AF: 0.0152

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.106 AC: 16113 AN: 152222 Hom.: 1121 Cov.: 32 AF XY: 0.105 AC XY: 7781 AN XY: 74432

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.0858

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0431

Gnomad4 FIN AF: 0.0537

Gnomad4 NFE AF: 0.0670

Gnomad4 OTH AF: 0.110

Alfa AF: 0.0712 Hom.: 572

Bravo AF: 0.116

Asia WGS AF: 0.0400 AC: 140 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.1
DANN	Benign	0.67

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

LitVar

Other links and lift over

dbSNP: rs11823543; hg19: chr11-116649135;