NM_198935.3:c.232-43G>A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_198935.3(SS18L1):​c.232-43G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.054 in 1,612,178 control chromosomes in the GnomAD database, including 3,042 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.078 (692 hom., cov: 32)
  • Exomes 𝑓: 0.052 (2350 hom.)
• Consequence: SS18L1 NM_198935.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0300
• Publications: 2 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: Genomics England PanelApp, ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 20-62161393-G-A is Benign according to our data. Variant chr20-62161393-G-A is described in ClinVar as [Benign]. Clinvar id is 1245616.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.0779 AC: 11812 AN: 151702 Hom.: 689 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.0363

Gnomad AMR AF: 0.0518

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.000777

Gnomad SAS AF: 0.0480

Gnomad FIN AF: 0.0189

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0506

Gnomad OTH AF: 0.0897

GnomAD2 exomes AF: 0.0508 AC: 12458 AN: 245030 AF XY: 0.0499

Gnomad AFR exome AF: 0.156

Gnomad AMR exome AF: 0.0371

Gnomad ASJ exome AF: 0.0978

Gnomad EAS exome AF: 0.000946

Gnomad FIN exome AF: 0.0206

Gnomad NFE exome AF: 0.0516

Gnomad OTH exome AF: 0.0526

GnomAD4 exome AF: 0.0516 AC: 75294 AN: 1460358 Hom.: 2350 Cov.: 32 AF XY: 0.0513 AC XY: 37280 AN XY: 726470

African (AFR) AF: 0.165 AC: 5525 AN: 33480

American (AMR) AF: 0.0396 AC: 1770 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.0945 AC: 2469 AN: 26130

East Asian (EAS) AF: 0.000705 AC: 28 AN: 39694

South Asian (SAS) AF: 0.0463 AC: 3989 AN: 86196

European-Finnish (FIN) AF: 0.0216 AC: 1127 AN: 52164

Middle Eastern (MID) AF: 0.0813 AC: 469 AN: 5766

European-Non Finnish (NFE) AF: 0.0508 AC: 56455 AN: 1111856

Other (OTH) AF: 0.0574 AC: 3462 AN: 60364

GnomAD4 genome AF: 0.0780 AC: 11835 AN: 151820 Hom.: 692 Cov.: 32 AF XY: 0.0749 AC XY: 5557 AN XY: 74158

African (AFR) AF: 0.158 AC: 6545 AN: 41376

American (AMR) AF: 0.0517 AC: 789 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 379 AN: 3468

East Asian (EAS) AF: 0.000584 AC: 3 AN: 5136

South Asian (SAS) AF: 0.0485 AC: 232 AN: 4784

European-Finnish (FIN) AF: 0.0189 AC: 200 AN: 10560

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0506 AC: 3441 AN: 67938

Other (OTH) AF: 0.0888 AC: 187 AN: 2106

Alfa AF: 0.0503 Hom.: 79

Bravo AF: 0.0839

Asia WGS AF: 0.0380 AC: 135 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 16, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.1
DANN	Benign	0.83
PhyloP100		0.030
PromoterAI		0.0047	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs60991008; hg19: chr20-60736449;