20-62161393-G-T

Variant names:

• chr20-62161393-G-T
• rs60991008
• NM_198935.3:c.232-43G>T

Variant summary

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

The NM_198935.3(SS18L1):​c.232-43G>T variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: SS18L1 NM_198935.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0300

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 (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SS18L1	NM_198935.3	c.232-43G>T		intron_variant	Intron 3 of 10	ENST00000331758.8	NP_945173.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SS18L1	ENST00000331758.8	c.232-43G>T		intron_variant	Intron 3 of 10	1	NM_198935.3	ENSP00000333012.3
SS18L1	ENST00000450482.5	c.241-43G>T		intron_variant	Intron 4 of 4	5		ENSP00000398634.1
SS18L1	ENST00000370848.8	c.-58G>T		upstream_gene_variant		1		ENSP00000359885.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000659 AC: 1 AN: 151848 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74172

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000656

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.1
DANN	Benign	0.81

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: rs60991008; hg19: chr20-60736449;