rs587777633

Variant names:

• chr20-62161573-T-G
• rs587777633
• NM_198935.3:c.369T>G

Your query was ambiguous. Multiple possible variants found:

• chr20-62161573-T-G
• chr20-62161573-T-A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001301778.2(SS18L1):​c.-25T>G variant causes a 5 prime UTR premature start codon gain 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. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SS18L1 NM_001301778.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -0.354
• Publications: 8 publications found

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]

SS18L1 Gene-Disease associations (from GenCC):

• amyotrophic lateral sclerosis

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: ClinGen, Genomics England PanelApp

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001301778.2. 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
	SS18L1	NM_198935.3	MANE Select	c.369T>G	p.Ile123Met	missense	Exon 4 of 11	NP_945173.1	O75177-1
	SS18L1	NM_001301778.2		c.-25T>G		5_prime_UTR_premature_start_codon_gain	Exon 5 of 12	NP_001288707.1	O75177-4
	SS18L1	NM_001301778.2		c.-25T>G		5_prime_UTR	Exon 5 of 12	NP_001288707.1	O75177-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SS18L1	ENST00000331758.8	TSL:1 MANE Select	c.369T>G	p.Ile123Met	missense	Exon 4 of 11	ENSP00000333012.3	O75177-1
	SS18L1	ENST00000370848.8	TSL:1	c.123T>G	p.Ile41Met	missense	Exon 1 of 9	ENSP00000359885.5	O75177-3
	SS18L1	ENST00000450482.5	TSL:5	c.378T>G	p.Ile126Met	missense	Exon 5 of 5	ENSP00000398634.1	Q9BR54

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

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
DEOGEN2	Benign	0.026	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.060	D
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.57	N
PhyloP100		-0.35
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	0.65	N
REVEL	Benign	0.098
Sift	Benign	0.52	T
Sift4G	Benign	0.71	T
Polyphen		0.21	B
Vest4		0.35
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
PromoterAI		-0.093	Neutral
Varity_R		0.13
gMVP		0.26
Mutation Taster		=6/94	disease causing

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

Other links and lift over

dbSNP: rs587777633; hg19: chr20-60736629;