1-182453967-G-A

Variant names:

• chr1-182453967-G-A
• NM_001137669.2:c.23G>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.23G>A​(p.Gly8Asp) variant causes a missense 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. 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)
• Consequence: RGSL1 NM_001137669.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.298

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=0.060358375).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGSL1	NM_001137669.2	c.23G>A	p.Gly8Asp	missense_variant	Exon 2 of 22	ENST00000294854.13	NP_001131141.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGSL1	ENST00000294854.13	c.23G>A	p.Gly8Asp	missense_variant	Exon 2 of 22	1	NM_001137669.2	ENSP00000457748.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.23G>A (p.G8D) alteration is located in exon 2 (coding exon 2) of the RGSL1 gene. This alteration results from a G to A substitution at nucleotide position 23, causing the glycine (G) at amino acid position 8 to be replaced by an aspartic acid (D). 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	0.29
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	12
DANN	Benign	0.87
DEOGEN2	Benign	0.0081	T
FATHMM_MKL	Benign	0.076	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.060	T
MutationAssessor	Benign	1.6	L
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.1	N
Sift	Benign	0.052	T
Sift4G	Benign	0.10	T
Polyphen		0.089	B
Vest4		0.18
MVP		0.13
GERP RS		0.91
Varity_R		0.064
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-182423102; COSMIC: COSV54262620; COSMIC: COSV54262620;