1-15660215-G-A

Position:

chr1-15660215-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006511.3(RSC1A1):c.347G>A(p.Arg116Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000088 in 1,614,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000094 ( 0 hom. )

Consequence

RSC1A1
NM_006511.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.399

Variant links:

Genes affected

RSC1A1 (HGNC:10458): (regulator of solute carriers 1) The protein encoded by this intronless gene inhibits the expression of the solute carrier family 5 (sodium/glucose cotransporter), member 1 gene (SLC5A1) and downregulates exocytosis of the SLC5A1 protein. The encoded protein is sometimes found coating the trans-Golgi network and other times is localized to the nucleus, depending on the cell cycle stage. This protein also inhibits the expression of solute carrier family 22 (organic cation transporter), member 2 (SLC22A2). [provided by RefSeq, Dec 2015]

RSC1A1 links:

DDI2 (HGNC:24578): (DNA damage inducible 1 homolog 2) Enables aspartic-type endopeptidase activity; identical protein binding activity; and ubiquitin binding activity. Involved in several processes, including cellular response to hydroxyurea; proteolysis; and regulation of DNA stability. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

DDI2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.02183792).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSC1A1	NM_006511.3 linkuse as main transcript	c.347G>A	p.Arg116Lys	missense_variant	1/1	ENST00000345034.2	NP_006502.1
DDI2	NM_032341.5 linkuse as main transcript	c.*425G>A		3_prime_UTR_variant	10/10	ENST00000480945.6	NP_115717.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RSC1A1	ENST00000345034.2 linkuse as main transcript	c.347G>A	p.Arg116Lys	missense_variant	1/1		NM_006511.3	ENSP00000341963	P1
DDI2	ENST00000480945.6 linkuse as main transcript	c.*425G>A		3_prime_UTR_variant	10/10	2	NM_032341.5	ENSP00000417748	P1	Q5TDH0-1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000124

AC:

AN:

250950

Hom.:

AF XY:

0.0000959

AC XY:

AN XY:

135608

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000405

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000141

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000944

AC:

138

AN:

1461880

Hom.:

Cov.:

AF XY:

0.0000880

AC XY:

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000335

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000103

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152190

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000102

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000988

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 08, 2023

The c.347G>A (p.R116K) alteration is located in exon 1 (coding exon 1) of the RSC1A1 gene. This alteration results from a G to A substitution at nucleotide position 347, causing the arginine (R) at amino acid position 116 to be replaced by a lysine (K). 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

Benign

0.072

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.78

CADD

Benign

6.7

DANN

Benign

0.53

DEOGEN2

Benign

0.13

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.091

LIST_S2

Benign

0.50

M_CAP

Benign

0.0052

MetaRNN

Benign

0.022

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

MutationTaster

Benign

0.93

D;N

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.40

REVEL

Benign

0.035

Sift

Benign

0.61

Sift4G

Benign

1.0

Polyphen

0.0010

Vest4

0.042

MutPred

0.20

Gain of ubiquitination at R116 (P = 0.0025);

MVP

0.099

MPC

0.032

ClinPred

0.013

GERP RS

-0.57

Varity_R

0.027

gMVP

0.12

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over