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GeneBe

1-15660482-A-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_006511.3(RSC1A1):c.614A>T(p.Asn205Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00274 in 1,614,096 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0019 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0028 ( 10 hom. )

Consequence

RSC1A1
NM_006511.3 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0720
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]
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.006115496).
BS2
High Homozygotes in GnomAdExome4 at 10 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RSC1A1NM_006511.3 linkuse as main transcriptc.614A>T p.Asn205Ile missense_variant 1/1 ENST00000345034.2
DDI2NM_032341.5 linkuse as main transcriptc.*692A>T 3_prime_UTR_variant 10/10 ENST00000480945.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RSC1A1ENST00000345034.2 linkuse as main transcriptc.614A>T p.Asn205Ile missense_variant 1/1 NM_006511.3 P1
DDI2ENST00000480945.6 linkuse as main transcriptc.*692A>T 3_prime_UTR_variant 10/102 NM_032341.5 P1Q5TDH0-1

Frequencies

GnomAD3 genomes
AF:
0.00194
AC:
295
AN:
152254
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000362
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00105
Gnomad ASJ
AF:
0.00202
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00124
Gnomad FIN
AF:
0.00132
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00344
Gnomad OTH
AF:
0.00144
GnomAD3 exomes
AF:
0.00190
AC:
475
AN:
250534
Hom.:
0
AF XY:
0.00189
AC XY:
256
AN XY:
135394
show subpopulations
Gnomad AFR exome
AF:
0.000555
Gnomad AMR exome
AF:
0.000696
Gnomad ASJ exome
AF:
0.00139
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000753
Gnomad FIN exome
AF:
0.00176
Gnomad NFE exome
AF:
0.00311
Gnomad OTH exome
AF:
0.00246
GnomAD4 exome
AF:
0.00283
AC:
4131
AN:
1461724
Hom.:
10
Cov.:
32
AF XY:
0.00273
AC XY:
1988
AN XY:
727138
show subpopulations
Gnomad4 AFR exome
AF:
0.000418
Gnomad4 AMR exome
AF:
0.000694
Gnomad4 ASJ exome
AF:
0.00126
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000696
Gnomad4 FIN exome
AF:
0.00146
Gnomad4 NFE exome
AF:
0.00338
Gnomad4 OTH exome
AF:
0.00245
GnomAD4 genome
AF:
0.00194
AC:
295
AN:
152372
Hom.:
0
Cov.:
33
AF XY:
0.00166
AC XY:
124
AN XY:
74522
show subpopulations
Gnomad4 AFR
AF:
0.000361
Gnomad4 AMR
AF:
0.00105
Gnomad4 ASJ
AF:
0.00202
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00124
Gnomad4 FIN
AF:
0.00132
Gnomad4 NFE
AF:
0.00344
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.00309
Hom.:
0
Bravo
AF:
0.00167
TwinsUK
AF:
0.00297
AC:
11
ALSPAC
AF:
0.00337
AC:
13
ESP6500AA
AF:
0.000681
AC:
3
ESP6500EA
AF:
0.00186
AC:
16
ExAC
AF:
0.00185
AC:
224
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.00365
EpiControl
AF:
0.00273

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 submitterclinical testingAmbry GeneticsSep 08, 2023The c.614A>T (p.N205I) alteration is located in exon 1 (coding exon 1) of the RSC1A1 gene. This alteration results from a A to T substitution at nucleotide position 614, causing the asparagine (N) at amino acid position 205 to be replaced by an isoleucine (I). 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
0.11
BayesDel_addAF
Benign
-0.54
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
16
DANN
Uncertain
0.98
DEOGEN2
Uncertain
0.47
T
Eigen
Benign
-0.52
Eigen_PC
Benign
-0.56
FATHMM_MKL
Benign
0.070
N
LIST_S2
Benign
0.53
T
M_CAP
Benign
0.0087
T
MetaRNN
Benign
0.0061
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.5
L
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.30
T
PROVEAN
Uncertain
-4.2
D
REVEL
Benign
0.044
Sift
Uncertain
0.010
D
Sift4G
Uncertain
0.022
D
Polyphen
0.69
P
Vest4
0.21
MVP
0.37
MPC
0.17
ClinPred
0.021
T
GERP RS
0.79
Varity_R
0.13
gMVP
0.12

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

LitVar

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

Other links and lift over

dbSNP: rs142452950; hg19: chr1-15986977; API