Genetic Variant RGSL1:p.Thr10Ile (chr1-182453973-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001137669.2(RGSL1):c.29C>T(p.Thr10Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,522,984 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

RGSL1
NM_001137669.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.54

Publications

0 publications found

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.35213822).

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.29C>T	p.Thr10Ile	missense	Exon 2 of 22	NP_001131141.1	A5PLK6-1
	RGSL1	NM_001366934.1		c.29C>T	p.Thr10Ile	missense	Exon 2 of 23	NP_001353863.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RGSL1	ENST00000294854.13	TSL:1 MANE Select	c.29C>T	p.Thr10Ile	missense	Exon 2 of 22	ENSP00000457748.1	A5PLK6-1
RGSL1	ENST00000437548.5	TSL:5	c.-389C>T		5_prime_UTR	Exon 2 of 7	ENSP00000454969.1	H3BNR3
RGSL1	ENST00000634723.1	TSL:5	c.-278C>T		5_prime_UTR	Exon 3 of 7	ENSP00000489611.1	A0A0U1RRN0

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000632

AC:

AN:

158146

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000164

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000117

AC:

AN:

1370846

Hom.:

Cov.:

AF XY:

0.0000162

AC XY:

AN XY:

678002

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31032

American (AMR)

AF:

0.00

AC:

AN:

35640

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25032

East Asian (EAS)

AF:

0.00

AC:

AN:

35590

South Asian (SAS)

AF:

0.00

AC:

AN:

78672

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49066

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5634

European-Non Finnish (NFE)

AF:

0.0000152

AC:

AN:

1053150

Other (OTH)

AF:

0.00

AC:

AN:

57030

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.413

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152138

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41418

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10584

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.67

BayesDel_addAF

Benign

-0.065

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.75

M_CAP

Benign

0.077

MetaRNN

Benign

0.35

MutationAssessor

Uncertain

2.5

PhyloP100

1.5

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-2.3

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.42

MVP

0.17

GERP RS

5.2

Varity_R

0.26

gMVP

0.69

Mutation Taster

=88/12

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over