Genetic Variant NM_006511.3:c.760G>A (chr1-15660628-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006511.3(RSC1A1):c.760G>A(p.Ala254Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A254P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

RSC1A1
NM_006511.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.737

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.117036134).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006511.3. 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
	RSC1A1	NM_006511.3	MANE Select	c.760G>A	p.Ala254Thr	missense	Exon 1 of 1	NP_006502.1	Q92681
	DDI2	NM_032341.5	MANE Select	c.*838G>A		3_prime_UTR	Exon 10 of 10	NP_115717.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RSC1A1	ENST00000345034.2	TSL:6 MANE Select	c.760G>A	p.Ala254Thr	missense	Exon 1 of 1	ENSP00000341963.1	Q92681
DDI2	ENST00000480945.6	TSL:2 MANE Select	c.*838G>A		3_prime_UTR	Exon 10 of 10	ENSP00000417748.1	Q5TDH0-1
DDI2	ENST00000711098.1		c.1975G>A	p.Ala659Thr	missense	Exon 9 of 9	ENSP00000518576.1	A0AA34QVL7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461824

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727210

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86240

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53380

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000719

AC:

AN:

1112008

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.28

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.71

M_CAP

Benign

0.0042

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

PhyloP100

0.74

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.3

REVEL

Benign

0.068

Sift

Benign

0.11

Sift4G

Benign

0.21

Polyphen

0.76

Vest4

0.19

MutPred

0.19

Loss of helix (P = 0.0376)

MVP

0.20

MPC

0.093

ClinPred

0.27

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.054

gMVP

0.18

Mutation Taster

=99/1

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over