1-15659912-G-T

Variant names:

• chr1-15659912-G-T
• rs761070050
• NM_006511.3:c.44G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006511.3(RSC1A1):​c.44G>T​(p.Arg15Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,456 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. R15H) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RSC1A1 NM_006511.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.910
• Publications: 0 publications found

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]

ACMG classification

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=0.058341086).

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.44G>T	p.Arg15Leu	missense	Exon 1 of 1	NP_006502.1	Q92681
	DDI2	NM_032341.5	MANE Select	c.*122G>T		3_prime_UTR	Exon 10 of 10	NP_115717.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSC1A1	ENST00000345034.2	TSL:6 MANE Select	c.44G>T	p.Arg15Leu	missense	Exon 1 of 1	ENSP00000341963.1	Q92681
	DDI2	ENST00000480945.6	TSL:2 MANE Select	c.*122G>T		3_prime_UTR	Exon 10 of 10	ENSP00000417748.1	Q5TDH0-1
	DDI2	ENST00000711098.1		c.1259G>T	p.Arg420Leu	missense	Exon 9 of 9	ENSP00000518576.1	A0AA34QVL7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1453456 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 722928

African (AFR) AF: 0.00 AC: 0 AN: 33004

American (AMR) AF: 0.00 AC: 0 AN: 42150

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25490

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 84534

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53242

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5712

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109620

Other (OTH) AF: 0.00 AC: 0 AN: 60020

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.42	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.91
PrimateAI	Benign	0.20	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.14
Sift	Uncertain	0.027	D
Sift4G	Benign	0.081	T
Polyphen		0.044	B
Vest4		0.20
MutPred		0.16		Loss of phosphorylation at S17 (P = 0.072)
MVP		0.41
MPC		0.039
ClinPred		0.41	T
GERP RS		-1.6
PromoterAI		-0.0077	Neutral
Varity_R		0.077
gMVP		0.21
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs761070050; hg19: chr1-15986407;