X-63350506-ACT-A

Variant names:

• chrX-63350506-ACT-A
• NM_001012968.3:c.312_313delAG

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_001012968.3(SPIN4):​c.312_313delAG​(p.Arg104SerfsTer24) variant causes a frameshift change. The variant allele was found at a frequency of 0.000000911 in 1,098,200 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: SPIN4 NM_001012968.3 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.46

Genes affected

SPIN4 (HGNC:27040): (spindlin family member 4) Enables methylated histone binding activity. Predicted to be involved in regulation of transcription, DNA-templated. Predicted to be active in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

SPIN4-AS1 (HGNC:41177): (SPIN4 antisense RNA 1)

LINC01278 (HGNC:28090): (long intergenic non-protein coding RNA 1278)

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant X-63350506-ACT-A is Pathogenic according to our data. Variant chrX-63350506-ACT-A is described in ClinVar as [Pathogenic]. Clinvar id is 2671851.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPIN4	NM_001012968.3	c.312_313delAG	p.Arg104SerfsTer24	frameshift_variant	Exon 1 of 1	ENST00000374884.3	NP_001012986.2
SPIN4-AS1	NR_046739.1	n.298+778_298+779delTC		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPIN4	ENST00000374884.3	c.312_313delAG	p.Arg104SerfsTer24	frameshift_variant	Exon 1 of 1	6	NM_001012968.3	ENSP00000364018.3

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1098200 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 363554

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000119

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Lui-Jee-Baron syndrome Pathogenic:1

Dec 18, 2023

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-62570385;