NM_006511.3:c.494C>T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006511.3(RSC1A1):c.494C>T(p.Pro165Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,738 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. P165R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

RSC1A1
NM_006511.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.906

Publications

1 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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.025957614).

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.494C>T	p.Pro165Leu	missense	Exon 1 of 1	NP_006502.1	Q92681
	DDI2	NM_032341.5	MANE Select	c.*572C>T		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.494C>T	p.Pro165Leu	missense	Exon 1 of 1	ENSP00000341963.1	Q92681
DDI2	ENST00000480945.6	TSL:2 MANE Select	c.*572C>T		3_prime_UTR	Exon 10 of 10	ENSP00000417748.1	Q5TDH0-1
DDI2	ENST00000711098.1		c.1709C>T	p.Pro570Leu	missense	Exon 9 of 9	ENSP00000518576.1	A0AA34QVL7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000401

AC:

AN:

249660

AF XY:

0.00000739

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000887

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461738

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727182

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33464

American (AMR)

AF:

0.00

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86242

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53376

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000450

AC:

AN:

1111960

Other (OTH)

AF:

0.00

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

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.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.75

CADD

Benign

5.7

(source)

DANN

Benign

0.65

DEOGEN2

Benign

0.081

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.57

M_CAP

Benign

0.0025

MetaRNN

Benign

0.026

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-1.5

PhyloP100

0.91

PrimateAI

Benign

0.23

PROVEAN

Benign

2.0

REVEL

Benign

0.056

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.12

MutPred

0.073

Loss of glycosylation at S160 (P = 0.1879)

MVP

0.26

MPC

0.031

ClinPred

0.032

GERP RS

1.9

Varity_R

0.021

gMVP

0.074

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

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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