11-116776891-C-T

Variant names:

• chr11-116776891-C-T
• rs2160669
• NM_003904.5:c.*2034G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 29 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: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZPR1	NM_003904.5	MANE Select	c.*2034G>A		3_prime_UTR	Exon 14 of 14	NP_003895.1
	ZPR1	NM_001317086.2		c.*2034G>A		3_prime_UTR	Exon 13 of 13	NP_001304015.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZPR1	ENST00000227322.8	TSL:1 MANE Select	c.*2034G>A		3_prime_UTR	Exon 14 of 14	ENSP00000227322.3

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 14 AN: 14

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.942 AC: 39128 AN: 41548

American (AMR) AF: 0.877 AC: 13419 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.898 AC: 3118 AN: 3472

East Asian (EAS) AF: 0.767 AC: 3975 AN: 5182

South Asian (SAS) AF: 0.808 AC: 3902 AN: 4830

European-Finnish (FIN) AF: 0.917 AC: 9728 AN: 10614

Middle Eastern (MID) AF: 0.874 AC: 257 AN: 294

European-Non Finnish (NFE) AF: 0.927 AC: 63067 AN: 68034

Other (OTH) AF: 0.903 AC: 1908 AN: 2114

Alfa AF: 0.917 Hom.: 121847

Bravo AF: 0.914

Asia WGS AF: 0.803 AC: 2793 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.15
DANN	Benign	0.37
PhyloP100		-3.0

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: rs2160669; hg19: chr11-116647607;