NM_003904.5:c.333+167A>C

Variant names:

• chr11-116787315-T-G
• rs12285095
• NM_003904.5:c.333+167A>C

Variant summary

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

The NM_003904.5(ZPR1):​c.333+167A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0702 in 740,678 control chromosomes in the GnomAD database, including 2,338 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 0.096 (894 hom., cov: 33)
  • Exomes 𝑓: 0.064 (1444 hom.)
• Consequence: ZPR1 NM_003904.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.826

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZPR1	NM_003904.5	c.333+167A>C		intron_variant	Intron 2 of 13	ENST00000227322.8	NP_003895.1
ZPR1	NM_001317086.2	c.172-256A>C		intron_variant	Intron 1 of 12		NP_001304015.1
ZPR1	XM_047427804.1	c.333+167A>C		intron_variant	Intron 2 of 8		XP_047283760.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZPR1	ENST00000227322.8	c.333+167A>C		intron_variant	Intron 2 of 13	1	NM_003904.5	ENSP00000227322.3

Frequencies

GnomAD3 genomes AF: 0.0956 AC: 14539 AN: 152142 Hom.: 889 Cov.: 33

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.0740

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0449

Gnomad FIN AF: 0.0539

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0645

Gnomad OTH AF: 0.103

GnomAD4 exome AF: 0.0636 AC: 37426 AN: 588418 Hom.: 1444 Cov.: 8 AF XY: 0.0622 AC XY: 18860 AN XY: 303222

Gnomad4 AFR exome AF: 0.158

Gnomad4 AMR exome AF: 0.141

Gnomad4 ASJ exome AF: 0.0689

Gnomad4 EAS exome AF: 0.000723

Gnomad4 SAS exome AF: 0.0432

Gnomad4 FIN exome AF: 0.0617

Gnomad4 NFE exome AF: 0.0629

Gnomad4 OTH exome AF: 0.0733

GnomAD4 genome AF: 0.0957 AC: 14575 AN: 152260 Hom.: 894 Cov.: 33 AF XY: 0.0946 AC XY: 7043 AN XY: 74450

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.0740

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.0452

Gnomad4 FIN AF: 0.0539

Gnomad4 NFE AF: 0.0645

Gnomad4 OTH AF: 0.102

Alfa AF: 0.0905 Hom.: 100

Bravo AF: 0.105

Asia WGS AF: 0.0400 AC: 139 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.7
DANN	Benign	0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Publications

LitVar

Other links and lift over

dbSNP: rs12285095; hg19: chr11-116658031;