1-182474259-C-T

Position:

• chr1-182474259-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001137669.2(RGSL1):​c.1148C>T​(p.Pro383Leu) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P383T) has been classified 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: 3.35

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]

RGSL1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.861

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGSL1	NM_001137669.2	c.1148C>T	p.Pro383Leu	missense_variant	6/22	ENST00000294854.13	NP_001131141.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGSL1	ENST00000294854.13	c.1148C>T	p.Pro383Leu	missense_variant	6/22	1	NM_001137669.2	ENSP00000457748.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 08, 2024

The c.1148C>T (p.P383L) alteration is located in exon 6 (coding exon 6) of the RGSL1 gene. This alteration results from a C to T substitution at nucleotide position 1148, causing the proline (P) at amino acid position 383 to be replaced by a leucine (L). 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	0.45
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.86	D
M_CAP	Uncertain	0.14	D
MetaRNN	Pathogenic	0.86	D
MutationAssessor	Benign	1.8	L
PrimateAI	Benign	0.43	T
PROVEAN	Pathogenic	-5.2	D
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.82
MVP		0.41
GERP RS		5.0
Varity_R		0.34
gMVP		0.60

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-182443394;