20-62162589-C-T

Position:

• chr20-62162589-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_198935.3(SS18L1):​c.377-163C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.033 in 722,308 control chromosomes in the GnomAD database, including 3,450 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (2514 hom., cov: 33)
  • Exomes 𝑓: 0.015 (936 hom.)
• Consequence: SS18L1 NM_198935.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.497

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 20-62162589-C-T is Benign according to our data. Variant chr20-62162589-C-T is described in ClinVar as [Benign]. Clinvar id is 1271202.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SS18L1	NM_198935.3	c.377-163C>T		intron_variant		ENST00000331758.8	NP_945173.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SS18L1	ENST00000331758.8	c.377-163C>T		intron_variant		1	NM_198935.3	ENSP00000333012.3
SS18L1	ENST00000370848.8	c.131-163C>T		intron_variant		1		ENSP00000359885.5
SS18L1	ENST00000491916.1	n.42C>T		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15502 AN: 152122 Hom.: 2513 Cov.: 33

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0416

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00462

Gnomad OTH AF: 0.0708

GnomAD4 exome AF: 0.0145 AC: 8281 AN: 570068 Hom.: 936 Cov.: 8 AF XY: 0.0128 AC XY: 3744 AN XY: 291872

Gnomad4 AFR exome AF: 0.356

Gnomad4 AMR exome AF: 0.0286

Gnomad4 ASJ exome AF: 0.0149

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00139

Gnomad4 FIN exome AF: 0.00150

Gnomad4 NFE exome AF: 0.00417

Gnomad4 OTH exome AF: 0.0326

GnomAD4 genome AF: 0.102 AC: 15542 AN: 152240 Hom.: 2514 Cov.: 33 AF XY: 0.0987 AC XY: 7349 AN XY: 74448

Gnomad4 AFR AF: 0.347

Gnomad4 AMR AF: 0.0416

Gnomad4 ASJ AF: 0.0130

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.00132

Gnomad4 NFE AF: 0.00462

Gnomad4 OTH AF: 0.0701

Alfa AF: 0.0622 Hom.: 180

Bravo AF: 0.117

Asia WGS AF: 0.0260 AC: 91 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 21, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	9.9
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: rs73915599; hg19: chr20-60737645;