chr1-182473713-C-A

Variant names:

• chr1-182473713-C-A
• rs1170253575
• NM_001137669.2:c.602C>A

Variant summary

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

The NM_001137669.2(RGSL1):​c.602C>A​(p.Thr201Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,500 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: RGSL1 NM_001137669.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.380

Genes affected

RGSL1 (HGNC:18636): (regulator of G protein signaling like 1) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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 (MetaRNN=0.06753296).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGSL1	NM_001137669.2	c.602C>A	p.Thr201Asn	missense_variant	Exon 6 of 22	ENST00000294854.13	NP_001131141.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGSL1	ENST00000294854.13	c.602C>A	p.Thr201Asn	missense_variant	Exon 6 of 22	1	NM_001137669.2	ENSP00000457748.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000628 AC: 1 AN: 159174 Hom.: 0 AF XY: 0.0000120 AC XY: 1 AN XY: 83596

Gnomad AFR exome AF: 0.000112

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399500 Hom.: 0 Cov.: 30 AF XY: 0.00000145 AC XY: 1 AN XY: 690258

Gnomad4 AFR exome AF: 0.0000317

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000189

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 21, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.602C>A (p.T201N) alteration is located in exon 6 (coding exon 6) of the RGSL1 gene. This alteration results from a C to A substitution at nucleotide position 602, causing the threonine (T) at amino acid position 201 to be replaced by an asparagine (N). 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	Benign	0.095
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.14
DANN	Benign	0.92
DEOGEN2	Benign	0.00081	.;.;T
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.51	T;T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.068	T;T;T
MutationAssessor	Benign	0.55	.;.;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.070	.;.;N
Sift	Benign	0.27	.;.;T
Sift4G	Benign	0.15	T;T;T
Polyphen		0.0010	.;.;B
Vest4		0.048
MVP		0.14
GERP RS		-2.8
Varity_R		0.062
gMVP		0.18

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: rs1170253575; hg19: chr1-182442848;