Variant 18-26032532-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001007559.3(SS18):c.1097G>C(p.Gly366Ala) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000000684 in 1,460,942 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: 6.8e-7 ( 0 hom. )

Consequence

SS18
NM_001007559.3 missense, splice_region

Scores

Splicing: ADA: 0.8883

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.71

Variant links:

Genes affected

SS18 (HGNC:11340): (SS18 subunit of BAF chromatin remodeling complex) Enables nuclear receptor coactivator activity. Involved in positive regulation of transcription by RNA polymerase II. Part of SWI/SNF complex. Implicated in synovial sarcoma. [provided by Alliance of Genome Resources, Apr 2022]

SS18 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SS18	NM_001007559.3 linkuse as main transcript	c.1097G>C	p.Gly366Ala	missense_variant, splice_region_variant	10/11	ENST00000415083.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SS18	ENST00000415083.7 linkuse as main transcript	c.1097G>C	p.Gly366Ala	missense_variant, splice_region_variant	10/11	1	NM_001007559.3	A1	Q15532-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250542

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135412

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000291

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1460942

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726828

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jan 10, 2022

The c.1097G>C (p.G366A) alteration is located in exon 10 (coding exon 10) of the SS18 gene. This alteration results from a G to C substitution at nucleotide position 1097, causing the glycine (G) at amino acid position 366 to be replaced by an alanine (A). 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

0.15

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.38

Cadd

Pathogenic

Dann

Uncertain

0.98

DEOGEN2

Benign

0.31

T;T;.

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.10

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.93

D;D;D

M_CAP

Benign

0.034

MetaRNN

Benign

0.22

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.83

L;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Pathogenic

0.86

REVEL

Benign

0.11

Sift4G

Benign

0.14

T;T;T

Polyphen

0.0010

B;.;.

Vest4

0.60

MutPred

0.22

Gain of sheet (P = 0.0344);.;.;

MVP

0.23

MPC

0.30

ClinPred

0.36

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.27

gMVP

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.89

dbscSNV1_RF

Pathogenic

0.83

SpliceAI score (max)

0.28

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.28

Position offset: -47

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