11-116778201-G-C

Variant names:

• chr11-116778201-G-C
• rs964184
• NM_003904.5:c.*724C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003904.5(ZPR1):​c.*724C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.823 in 152,238 control chromosomes in the GnomAD database, including 51,799 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 0.82 (51773 hom., cov: 32)
  • Exomes 𝑓: 0.88 (26 hom.)
• Consequence: ZPR1 NM_003904.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.346
• Publications: 508 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.856 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.*724C>G		3_prime_UTR	Exon 14 of 14	NP_003895.1
	ZPR1	NM_001317086.2		c.*724C>G		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.*724C>G		3_prime_UTR	Exon 14 of 14	ENSP00000227322.3
	ZPR1	ENST00000444935.5	TSL:5	c.*724C>G		3_prime_UTR	Exon 13 of 13	ENSP00000390391.1
	ZPR1	ENST00000429220.5	TSL:5	c.*724C>G		3_prime_UTR	Exon 12 of 12	ENSP00000394495.1

Frequencies

GnomAD3 genomes AF: 0.823 AC: 125152 AN: 152052 Hom.: 51754 Cov.: 32

Gnomad AFR AF: 0.791

Gnomad AMI AF: 0.773

Gnomad AMR AF: 0.752

Gnomad ASJ AF: 0.824

Gnomad EAS AF: 0.768

Gnomad SAS AF: 0.766

Gnomad FIN AF: 0.863

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.862

Gnomad OTH AF: 0.808

GnomAD4 exome AF: 0.882 AC: 60 AN: 68 Hom.: 26 Cov.: 0 AF XY: 0.909 AC XY: 40 AN XY: 44

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AF: 1.00 AC: 2 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.833 AC: 5 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.870 AC: 47 AN: 54

Other (OTH) AF: 1.00 AC: 4 AN: 4

GnomAD4 genome AF: 0.823 AC: 125222 AN: 152170 Hom.: 51773 Cov.: 32 AF XY: 0.821 AC XY: 61051 AN XY: 74404

African (AFR) AF: 0.791 AC: 32809 AN: 41484

American (AMR) AF: 0.752 AC: 11499 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.824 AC: 2856 AN: 3466

East Asian (EAS) AF: 0.767 AC: 3974 AN: 5182

South Asian (SAS) AF: 0.765 AC: 3691 AN: 4822

European-Finnish (FIN) AF: 0.863 AC: 9146 AN: 10596

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.862 AC: 58623 AN: 68008

Other (OTH) AF: 0.804 AC: 1697 AN: 2112

Alfa AF: 0.852 Hom.: 30562

Bravo AF: 0.813

Asia WGS AF: 0.765 AC: 2662 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.48
DANN	Benign	0.42
PhyloP100		-0.35
Mutation Taster		=100/0	polymorphism (auto)

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: rs964184; hg19: chr11-116648917;