Genetic Variant NM_001137669.2:c.455T>C (chr1-182472549-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001137669.2(RGSL1):c.455T>C(p.Met152Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000347 in 1,527,354 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000034 ( 1 hom. )

Consequence

RGSL1
NM_001137669.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.414

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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.024933875).

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.455T>C	p.Met152Thr	missense	Exon 5 of 22	NP_001131141.1	A5PLK6-1
	RGSL1	NM_001366934.1		c.560T>C	p.Met187Thr	missense	Exon 6 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.455T>C	p.Met152Thr	missense	Exon 5 of 22	ENSP00000457748.1	A5PLK6-1
RGSL1	ENST00000634679.1	TSL:5	c.98T>C	p.Met33Thr	missense	Exon 2 of 3	ENSP00000489502.1	A0A0U1RRF6
RGSL1	ENST00000634758.1	TSL:5	c.-68-1026T>C		intron	N/A	ENSP00000488942.1	A0A0U1RQD8

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152128

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:

0.00116

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000173

AC:

AN:

149864

AF XY:

0.000127

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00236

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000342

AC:

AN:

1375226

Hom.:

Cov.:

AF XY:

0.0000252

AC XY:

AN XY:

674522

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31156

American (AMR)

AF:

0.00

AC:

AN:

34000

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24702

East Asian (EAS)

AF:

0.00122

AC:

AN:

35132

South Asian (SAS)

AF:

0.00

AC:

AN:

75722

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49024

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5590

European-Non Finnish (NFE)

AF:

0.00000282

AC:

AN:

1062950

Other (OTH)

AF:

0.0000176

AC:

AN:

56950

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

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:

0.0000394

AC:

AN:

152128

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41422

American (AMR)

AF:

0.00

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00116

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68006

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

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:

0.0000680

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

Benign

0.12

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.013

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.51

M_CAP

Benign

0.013

MetaRNN

Benign

0.025

MutationAssessor

Benign

1.4

PhyloP100

0.41

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.9

Sift

Benign

0.12

Sift4G

Benign

0.32

Polyphen

0.030

Vest4

0.33

MVP

0.16

GERP RS

2.2

Varity_R

0.16

gMVP

0.13

Mutation Taster

=97/3

polymorphism

(source)

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

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