rs1471031064

Variant names:

• chr20-62159959-G-A
• rs1471031064
• NM_198935.3:c.229G>A

Your query was ambiguous. Multiple possible variants found:

• chr20-62159959-G-A
• chr20-62159959-G-C
• chr20-62159959-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_198935.3(SS18L1):​c.229G>A​(p.Ala77Thr) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: SS18L1 NM_198935.3 missense, splice_region
• Scores: Splicing: ADA: 0.9408
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.37

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SS18L1	NM_198935.3	c.229G>A	p.Ala77Thr	missense_variant, splice_region_variant	Exon 3 of 11	ENST00000331758.8	NP_945173.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SS18L1	ENST00000331758.8	c.229G>A	p.Ala77Thr	missense_variant, splice_region_variant	Exon 3 of 11	1	NM_198935.3	ENSP00000333012.3
SS18L1	ENST00000450482.5	c.238G>A	p.Ala80Thr	missense_variant, splice_region_variant	Exon 4 of 5	5		ENSP00000398634.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 30

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.229G>A (p.A77T) alteration is located in exon 3 (coding exon 3) of the SS18L1 gene. This alteration results from a G to A substitution at nucleotide position 229, causing the alanine (A) at amino acid position 77 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Pathogenic	31
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.28	.;T
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Benign	0.051	D
MetaRNN	Uncertain	0.45	T;T
MetaSVM	Benign	-0.64	T
MutationAssessor	Uncertain	2.2	.;M
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-2.1	N;N
REVEL	Benign	0.29
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.019	D;T
Polyphen		1.0	.;D
Vest4		0.75
MutPred		0.17		.;Gain of glycosylation at A77 (P = 0.0054);
MVP		0.39
MPC		0.98
ClinPred		0.98	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.22
gMVP		0.76

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.94
dbscSNV1_RF	Pathogenic	0.78
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: rs1471031064; hg19: chr20-60735015;