Variant 14-77720805-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_012245.3(SNW1):c.1154A>G(p.Asn385Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000684 in 1,461,226 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

SNW1
NM_012245.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.26

Variant links:

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]

SNW1 links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.28516036).

BS2

High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNW1	NM_012245.3 linkuse as main transcript	c.1154A>G	p.Asn385Ser	missense_variant	12/14	ENST00000261531.12	NP_036377.1	Q13573
SNW1	NM_001318844.2 linkuse as main transcript	c.1154A>G	p.Asn385Ser	missense_variant	12/13		NP_001305773.1	G3V3A4
SNW1	XM_047431112.1 linkuse as main transcript	c.1057A>G	p.Ile353Val	missense_variant	11/12		XP_047287068.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNW1	ENST00000261531.12 linkuse as main transcript	c.1154A>G	p.Asn385Ser	missense_variant	12/14	1	NM_012245.3	ENSP00000261531.8		Q13573

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

250966

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135628

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461226

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

726954

show subpopulations

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:

0.00000810

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 01, 2022

The c.1154A>G (p.N385S) alteration is located in exon 12 (coding exon 12) of the SNW1 gene. This alteration results from a A to G substitution at nucleotide position 1154, causing the asparagine (N) at amino acid position 385 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.085

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.31

T;T;T

Eigen

Benign

0.098

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.94

LIST_S2

Pathogenic

0.99

D;D;D

M_CAP

Benign

0.0094

MetaRNN

Benign

0.29

T;T;T

MetaSVM

Benign

-0.64

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-0.47

N;N;N

REVEL

Uncertain

0.40

Sift

Benign

0.094

T;D;D

Sift4G

Uncertain

0.028

D;T;D

Polyphen

0.043

B;.;B

Vest4

0.31

MutPred

0.30

Gain of phosphorylation at N385 (P = 0.0075);.;Gain of phosphorylation at N385 (P = 0.0075);

MVP

0.56

MPC

1.1

ClinPred

0.92

GERP RS

4.2

Varity_R

0.064

gMVP

0.17

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over