1-48229172-T-C

Variant names:

• chr1-48229172-T-C
• rs1046028615
• ENST00000236495.9:c.409T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001135181.2(SLC5A9):​c.409T>C​(p.Ser137Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,790 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLC5A9 NM_001135181.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.36
• Publications: 0 publications found

Genes affected

SLC5A9 (HGNC:22146): (solute carrier family 5 member 9) Predicted to enable glucose:sodium symporter activity. Predicted to be involved in sodium ion transport. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000272491 (HGNC:):

ACMG classification

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=0.11494017).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135181.2. 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
	SLC5A9	NM_001011547.3	MANE Select	c.340-123T>C		intron	N/A	NP_001011547.2	Q2M3M2-1
	SLC5A9	NM_001135181.2		c.409T>C	p.Ser137Pro	missense	Exon 4 of 15	NP_001128653.1	Q2M3M2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC5A9	ENST00000236495.9	TSL:1	c.409T>C	p.Ser137Pro	missense	Exon 4 of 15	ENSP00000236495.5	Q2M3M2-2
	SLC5A9	ENST00000438567.7	TSL:1 MANE Select	c.340-123T>C		intron	N/A	ENSP00000401730.2	Q2M3M2-1
	SLC5A9	ENST00000533824.5	TSL:1	c.402+7T>C		splice_region intron	N/A	ENSP00000431900.1	Q2M3M2-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461790 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727200

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111922

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	1.0
DANN	Benign	0.93
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.81	T
PhyloP100		-1.4
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.13	N
REVEL	Benign	0.11
Sift	Benign	0.11	T
Sift4G	Benign	0.16	T
Vest4		0.14
MutPred		0.61		Loss of catalytic residue at S137 (P = 0.0209)
MVP		0.055
MPC		0.26
ClinPred		0.065	T
GERP RS		-5.7
gMVP		0.85
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1046028615; hg19: chr1-48694844;