14-77754635-A-T

Variant names:

• chr14-77754635-A-T
• rs1477261
• NM_012245.3:c.168+332T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012245.3(SNW1):​c.168+332T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.818 in 151,898 control chromosomes in the GnomAD database, including 50,928 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 (50928 hom., cov: 29)
• Consequence: SNW1 NM_012245.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.232
• Publications: 4 publications found

Genes affected

SNW1 (HGNC:16696): (SNW domain containing 1) This gene, a member of the SNW gene family, encodes a coactivator that enhances transcription from some Pol II promoters. This coactivator can bind to the ligand-binding domain of the vitamin D receptor and to retinoid receptors to enhance vitamin D-, retinoic acid-, estrogen-, and glucocorticoid-mediated gene expression. It can also function as a splicing factor by interacting with poly(A)-binding protein 2 to directly control the expression of muscle-specific genes at the transcriptional level. Finally, the protein may be involved in oncogenesis since it interacts with a region of SKI oncoproteins that is required for transforming activity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

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 Gene-Disease associations (from GenCC):

• inborn mitochondrial metabolism disorder

  Inheritance: AR Classification: LIMITED Submitted by: PanelApp Australia
• mitochondrial encephalomyopathy

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012245.3. 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
	SNW1	NM_012245.3	MANE Select	c.168+332T>A		intron	N/A	NP_036377.1	Q13573
	SNW1	NM_001318844.2		c.168+332T>A		intron	N/A	NP_001305773.1	G3V3A4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNW1	ENST00000261531.12	TSL:1 MANE Select	c.168+332T>A		intron	N/A	ENSP00000261531.8	Q13573
	SNW1	ENST00000555761.5	TSL:2	c.168+332T>A		intron	N/A	ENSP00000451129.1	G3V3A4
	SNW1	ENST00000851821.1		c.168+332T>A		intron	N/A	ENSP00000521880.1

Frequencies

GnomAD3 genomes AF: 0.818 AC: 124127 AN: 151780 Hom.: 50880 Cov.: 29

Gnomad AFR AF: 0.791

Gnomad AMI AF: 0.854

Gnomad AMR AF: 0.821

Gnomad ASJ AF: 0.835

Gnomad EAS AF: 0.745

Gnomad SAS AF: 0.855

Gnomad FIN AF: 0.865

Gnomad MID AF: 0.850

Gnomad NFE AF: 0.827

Gnomad OTH AF: 0.837

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

GnomAD4 genome AF: 0.818 AC: 124231 AN: 151898 Hom.: 50928 Cov.: 29 AF XY: 0.818 AC XY: 60748 AN XY: 74266

African (AFR) AF: 0.791 AC: 32749 AN: 41392

American (AMR) AF: 0.822 AC: 12523 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.835 AC: 2896 AN: 3468

East Asian (EAS) AF: 0.746 AC: 3832 AN: 5140

South Asian (SAS) AF: 0.856 AC: 4113 AN: 4806

European-Finnish (FIN) AF: 0.865 AC: 9139 AN: 10560

Middle Eastern (MID) AF: 0.842 AC: 246 AN: 292

European-Non Finnish (NFE) AF: 0.827 AC: 56200 AN: 67982

Other (OTH) AF: 0.832 AC: 1754 AN: 2108

Alfa AF: 0.814 Hom.: 5895

Bravo AF: 0.814

Asia WGS AF: 0.793 AC: 2746 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.66
PhyloP100		-0.23
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1477261; hg19: chr14-78220978;