18-26057736-T-A

Position:

• chr18-26057736-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001007559.3(SS18):​c.238A>T​(p.Thr80Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: SS18 NM_001007559.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.83

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30425274).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SS18	NM_001007559.3	c.238A>T	p.Thr80Ser	missense_variant	4/11	ENST00000415083.7	NP_001007560.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SS18	ENST00000415083.7	c.238A>T	p.Thr80Ser	missense_variant	4/11	1	NM_001007559.3	ENSP00000414516.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 08, 2022

The c.238A>T (p.T80S) alteration is located in exon 4 (coding exon 4) of the SS18 gene. This alteration results from a A to T substitution at nucleotide position 238, causing the threonine (T) at amino acid position 80 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	0.071
BayesDel_addAF	Uncertain	0.038	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	23
DANN	Benign	0.92
DEOGEN2	Benign	0.29	T;T;.;T;T;.
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.78	T;T;T;T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.30	T;T;T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.5	M;.;M;.;.;.
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.8	.;N;N;.;.;.
REVEL	Benign	0.14
Sift	Uncertain	0.0050	.;D;D;.;.;.
Sift4G	Benign	0.73	T;T;T;.;.;T
Polyphen		1.0	D;.;.;.;.;.
Vest4		0.56
MutPred		0.17		Loss of glycosylation at T80 (P = 0.038);.;Loss of glycosylation at T80 (P = 0.038);.;.;.;
MVP		0.26
MPC		0.62
ClinPred		0.76	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.35
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr18-23637700;