rs587777633

chr20-62161573-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_198935.3(SS18L1):c.369T>G(p.Ile123Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SS18L1 NM_198935.3 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -0.354

Genes affected

SS18L1 (HGNC:15592): (SS18L1 subunit of BAF chromatin remodeling complex) This gene encodes a calcium-responsive transactivator which is an essential subunit of a neuron-specific chromatin-remodeling complex. The structure of this gene is similar to that of the SS18 gene. Mutations in this gene are involved in amyotrophic lateral sclerosis (ALS). Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2014]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03998977).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SS18L1	NM_198935.3	c.369T>G	p.Ile123Met	missense_variant	4/11	ENST00000331758.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SS18L1	ENST00000331758.8	c.369T>G	p.Ile123Met	missense_variant	4/11	1	NM_198935.3	P1
SS18L1	ENST00000370848.8	c.123T>G	p.Ile41Met	missense_variant	1/9	1
SS18L1	ENST00000450482.5	c.378T>G	p.Ile126Met	missense_variant	5/5	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

Jul 01, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
Cadd	Benign	4.2
Dann	Benign	0.63
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.63	T;T;T
M_CAP	Benign	0.060	D
MetaRNN	Benign	0.040	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.56	N;N;N
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	0.65	N;N;.
REVEL	Benign	0.098
Sift	Benign	0.52	T;T;.
Sift4G	Benign	0.71	T;T;T
Polyphen		0.21	.;B;.
Vest4		0.35, 0.74
MutPred		0.20		.;Loss of catalytic residue at I123 (P = 0.0444);.;
MVP		0.14
MPC		0.96
ClinPred		0.21	T
GERP RS		-1.1
Varity_R		0.13
gMVP		0.26

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

Other links and lift over

dbSNP: rs587777633; hg19: chr20-60736629;