1-182473713-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001137669.2(RGSL1):​c.602C>T​(p.Thr201Ile) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T201N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RGSL1 NM_001137669.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.380
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.048639655).

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.602C>T	p.Thr201Ile	missense	Exon 6 of 22	NP_001131141.1	A5PLK6-1
	RGSL1	NM_001366934.1		c.707C>T	p.Thr236Ile	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.602C>T	p.Thr201Ile	missense	Exon 6 of 22	ENSP00000457748.1	A5PLK6-1
	RGSL1	ENST00000634679.1	TSL:5	c.245C>T	p.Thr82Ile	missense	Exon 3 of 3	ENSP00000489502.1	A0A0U1RRF6
	RGSL1	ENST00000634758.1	TSL:5	c.71C>T	p.Thr24Ile	missense	Exon 2 of 2	ENSP00000488942.1	A0A0U1RQD8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.57
DANN	Benign	0.96
DEOGEN2	Benign	0.0019	T
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.049	T
MutationAssessor	Benign	-0.29	N
PhyloP100		-0.38
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.97	N
Sift	Benign	0.26	T
Sift4G	Benign	0.56	T
Polyphen		0.0010	B
Vest4		0.023
MVP		0.16
GERP RS		-2.8
Varity_R		0.040
gMVP		0.095
Mutation Taster		=97/3	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

dbSNP: rs1170253575; hg19: chr1-182442848;