chr11-116778201-G-C

Position:

• chr11-116778201-G-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.856 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZPR1	NM_003904.5	c.*724C>G		3_prime_UTR_variant	14/14	ENST00000227322.8	NP_003895.1
ZPR1	NM_001317086.2	c.*724C>G		3_prime_UTR_variant	13/13		NP_001304015.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZPR1	ENST00000227322.8	c.*724C>G		3_prime_UTR_variant	14/14	1	NM_003904.5	ENSP00000227322	P1
ZPR1	ENST00000429220.5	c.*724C>G		3_prime_UTR_variant	12/12	5		ENSP00000394495
ZPR1	ENST00000444935.5	c.*724C>G		3_prime_UTR_variant	13/13	5		ENSP00000390391

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

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 1.00

Gnomad4 FIN exome AF: 0.833

Gnomad4 NFE exome AF: 0.870

Gnomad4 OTH exome AF: 1.00

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

Gnomad4 AFR AF: 0.791

Gnomad4 AMR AF: 0.752

Gnomad4 ASJ AF: 0.824

Gnomad4 EAS AF: 0.767

Gnomad4 SAS AF: 0.765

Gnomad4 FIN AF: 0.863

Gnomad4 NFE AF: 0.862

Gnomad4 OTH AF: 0.804

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.48
DANN	Benign	0.42

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: rs964184; hg19: chr11-116648917;