rs6589566

chr11-116781707-G-Achr11-116781707-G-Cchr11-116781707-G-T

Variant summary

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

The NM_003904.5(ZPR1):c.1179+451C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.929 in 152,268 control chromosomes in the GnomAD database, including 65,948 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 0.93 (65948 hom., cov: 31)
• Consequence: ZPR1 NM_003904.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.185

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZPR1	NM_003904.5	c.1179+451C>T		intron_variant		ENST00000227322.8
ZPR1	NM_001317086.2	c.1017+451C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZPR1	ENST00000227322.8	c.1179+451C>T		intron_variant		1	NM_003904.5	P1
ZPR1	ENST00000429220.5	c.958+451C>T		intron_variant		5
ZPR1	ENST00000444935.5	c.1091+1212C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.929 AC: 141338 AN: 152150 Hom.: 65897 Cov.: 31

Gnomad AFR AF: 0.984

Gnomad AMI AF: 0.897

Gnomad AMR AF: 0.887

Gnomad ASJ AF: 0.910

Gnomad EAS AF: 0.770

Gnomad SAS AF: 0.809

Gnomad FIN AF: 0.917

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.929

Gnomad OTH AF: 0.918

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.929 AC: 141445 AN: 152268 Hom.: 65948 Cov.: 31 AF XY: 0.925 AC XY: 68885 AN XY: 74434

Gnomad4 AFR AF: 0.985

Gnomad4 AMR AF: 0.887

Gnomad4 ASJ AF: 0.910

Gnomad4 EAS AF: 0.769

Gnomad4 SAS AF: 0.809

Gnomad4 FIN AF: 0.917

Gnomad4 NFE AF: 0.929

Gnomad4 OTH AF: 0.913

Alfa AF: 0.922 Hom.: 17976

Bravo AF: 0.929

Asia WGS AF: 0.805 AC: 2802 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.54
Dann	Benign	0.38

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: rs6589566; hg19: chr11-116652423;