chr1-182473733-T-C

Variant names:

• chr1-182473733-T-C
• NM_001137669.2:c.622T>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001137669.2(RGSL1):​c.622T>C​(p.Cys208Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000186 in 1,399,470 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: RGSL1 NM_001137669.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.67
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001137669.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGSL1	NM_001137669.2	MANE Select	c.622T>C	p.Cys208Arg	missense	Exon 6 of 22	NP_001131141.1	A5PLK6-1
	RGSL1	NM_001366934.1		c.727T>C	p.Cys243Arg	missense	Exon 7 of 23	NP_001353863.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGSL1	ENST00000294854.13	TSL:1 MANE Select	c.622T>C	p.Cys208Arg	missense	Exon 6 of 22	ENSP00000457748.1	A5PLK6-1
	RGSL1	ENST00000634679.1	TSL:5	c.265T>C	p.Cys89Arg	missense	Exon 3 of 3	ENSP00000489502.1	A0A0U1RRF6
	RGSL1	ENST00000634758.1	TSL:5	c.91T>C	p.Cys31Arg	missense	Exon 2 of 2	ENSP00000488942.1	A0A0U1RQD8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000186 AC: 26 AN: 1399470 Hom.: 0 Cov.: 30 AF XY: 0.0000159 AC XY: 11 AN XY: 690234

African (AFR) AF: 0.00 AC: 0 AN: 31594

American (AMR) AF: 0.00 AC: 0 AN: 35708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25178

East Asian (EAS) AF: 0.00 AC: 0 AN: 35692

South Asian (SAS) AF: 0.00 AC: 0 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49338

Middle Eastern (MID) AF: 0.000351 AC: 2 AN: 5698

European-Non Finnish (NFE) AF: 0.0000222 AC: 24 AN: 1078980

Other (OTH) AF: 0.00 AC: 0 AN: 58046

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Uncertain	0.046	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.70	T
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.58	D
MutationAssessor	Uncertain	2.6	M
PhyloP100		4.7
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-4.3	D
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.81
MVP		0.48
GERP RS		5.1
Varity_R		0.84
gMVP		0.57
Mutation Taster		=86/14	polymorphism

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

hg19: chr1-182442868;