chr11-116783719-C-A

Variant names:

• chr11-116783719-C-A
• rs603446
• NM_003904.5:c.892-100G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003904.5(ZPR1):​c.892-100G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZPR1 NM_003904.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.642
• Publications: 62 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZPR1	NM_003904.5	MANE Select	c.892-100G>T		intron	N/A	NP_003895.1
	ZPR1	NM_001317086.2		c.730-100G>T		intron	N/A	NP_001304015.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZPR1	ENST00000227322.8	TSL:1 MANE Select	c.892-100G>T		intron	N/A	ENSP00000227322.3
	ZPR1	ENST00000900046.1		c.922-100G>T		intron	N/A	ENSP00000570105.1
	ZPR1	ENST00000900049.1		c.892-100G>T		intron	N/A	ENSP00000570108.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 716690 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 380646

African (AFR) AF: 0.00 AC: 0 AN: 18274

American (AMR) AF: 0.00 AC: 0 AN: 31898

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18318

East Asian (EAS) AF: 0.00 AC: 0 AN: 36050

South Asian (SAS) AF: 0.00 AC: 0 AN: 63466

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47340

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4178

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 461666

Other (OTH) AF: 0.00 AC: 0 AN: 35500

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.6
DANN	Benign	0.48
PhyloP100		-0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs603446; hg19: chr11-116654435;