11-116776891-C-T

Variant summary

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

The NM_003904.5(ZPR1):c.*2034G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.915 in 152,318 control chromosomes in the GnomAD database, including 63,919 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 0.91 (63912 hom., cov: 33)
  • Exomes 𝑓: 1.0 (7 hom.)
• Consequence: ZPR1 NM_003904.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.95

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZPR1	NM_003904.5	c.*2034G>A		3_prime_UTR_variant	14/14	ENST00000227322.8
ZPR1	NM_001317086.2	c.*2034G>A		3_prime_UTR_variant	13/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZPR1	ENST00000227322.8	c.*2034G>A		3_prime_UTR_variant	14/14	1	NM_003904.5	P1

Frequencies

GnomAD3 genomes AF: 0.915 AC: 139217 AN: 152186 Hom.: 63865 Cov.: 33

Gnomad AFR AF: 0.942

Gnomad AMI AF: 0.897

Gnomad AMR AF: 0.877

Gnomad ASJ AF: 0.898

Gnomad EAS AF: 0.768

Gnomad SAS AF: 0.808

Gnomad FIN AF: 0.917

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.927

Gnomad OTH AF: 0.907

GnomAD4 exome AF: 1.00 AC: 14 AN: 14 Hom.: 7 Cov.: 0 AF XY: 1.00 AC XY: 8 AN XY: 8

Gnomad4 NFE exome AF: 1.00

GnomAD4 genome AF: 0.915 AC: 139320 AN: 152304 Hom.: 63912 Cov.: 33 AF XY: 0.911 AC XY: 67867 AN XY: 74464

Gnomad4 AFR AF: 0.942

Gnomad4 AMR AF: 0.877

Gnomad4 ASJ AF: 0.898

Gnomad4 EAS AF: 0.767

Gnomad4 SAS AF: 0.808

Gnomad4 FIN AF: 0.917

Gnomad4 NFE AF: 0.927

Gnomad4 OTH AF: 0.903

Alfa AF: 0.915 Hom.: 21546

Bravo AF: 0.914

Asia WGS AF: 0.803 AC: 2793 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.15
Dann	Benign	0.37

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: rs2160669; hg19: chr11-116647607;