14-77715859-CATATT-C

Position:

• chr14-77715859-CATATT-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP5_Moderate

The NM_031210.6(SLIRP):​c.248_252delTTATA​(p.Ile83fs) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,074 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: SLIRP NM_031210.6 frameshift
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 7.36

Genes affected

SLIRP (HGNC:20495): (SRA stem-loop interacting RNA binding protein) Steroid receptor RNA activator (SRA, or SRA1; MIM 603819) is a complex RNA molecule containing multiple stable stem-loop structures that functions in coactivation of nuclear receptors. SLIRP interacts with stem-loop structure-7 of SRA (STR7) and modulates nuclear receptor transactivation (Hatchell et al., 2006 [PubMed 16762838]).[supplied by OMIM, Mar 2008]

SLIRP (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 14-77715859-CATATT-C is Pathogenic according to our data. Variant chr14-77715859-CATATT-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1027546.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-77715859-CATATT-C is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLIRP	NM_031210.6	c.248_252delTTATA	p.Ile83fs	frameshift_variant	3/4	ENST00000557342.6	NP_112487.1
SLIRP	NM_001267863.1	c.248_252delTTATA	p.Ile83fs	frameshift_variant	3/4		NP_001254792.1
SLIRP	NM_001267864.1	c.248_252delTTATA	p.Ile83fs	frameshift_variant	3/4		NP_001254793.1
SLIRP	NR_052025.2	n.368_372delTTATA		non_coding_transcript_exon_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLIRP	ENST00000557342.6	c.248_252delTTATA	p.Ile83fs	frameshift_variant	3/4	1	NM_031210.6	ENSP00000450909.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152074 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152074 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74258

Gnomad4 AFR AF: 0.0000242

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000756

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Mitochondrial encephalomyopathy Pathogenic:1

Likely pathogenic, criteria provided, single submitter

in vitro

Department of Toxicogenomics, Maastricht University

Nov 25, 2020

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs776989213; hg19: chr14-78182202;