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GeneBe

1-15660854-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_006511.3(RSC1A1):c.986A>G(p.Tyr329Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,856 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 Likely benign (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

RSC1A1
NM_006511.3 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.328
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 Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.03669718).
BP6
Variant 1-15660854-A-G is Benign according to our data. Variant chr1-15660854-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2510190.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RSC1A1NM_006511.3 linkuse as main transcriptc.986A>G p.Tyr329Cys missense_variant 1/1 ENST00000345034.2
DDI2NM_032341.5 linkuse as main transcriptc.*1064A>G 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.986A>G p.Tyr329Cys missense_variant 1/1 NM_006511.3 P1
DDI2ENST00000480945.6 linkuse as main transcriptc.*1064A>G 3_prime_UTR_variant 10/102 NM_032341.5 P1Q5TDH0-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000159
AC:
4
AN:
250940
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135628
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000116
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461856
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727222
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000894
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.0000151
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsApr 06, 2023This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.058
BayesDel_addAF
Benign
-0.53
T
BayesDel_noAF
Benign
-0.78
CADD
Benign
0.46
DANN
Benign
0.38
DEOGEN2
Benign
0.078
T
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.011
N
LIST_S2
Benign
0.42
T
M_CAP
Benign
0.0039
T
MetaRNN
Benign
0.037
T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.23
N
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.22
T
PROVEAN
Benign
1.8
N
REVEL
Benign
0.030
Sift
Benign
0.18
T
Sift4G
Benign
0.18
T
Polyphen
0.0
B
Vest4
0.060
MutPred
0.16
Loss of solvent accessibility (P = 0.0155);
MVP
0.092
MPC
0.035
ClinPred
0.041
T
GERP RS
-1.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.034
gMVP
0.049

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: rs754462646; hg19: chr1-15987349; API