chr1-48228875-A-G

Variant names:

• chr1-48228875-A-G
• rs1644202382
• NM_001011547.3:c.260A>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001011547.3(SLC5A9):​c.260A>G​(p.Asn87Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,552 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. N87I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SLC5A9 NM_001011547.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.31
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.802

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001011547.3. 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
	SLC5A9	NM_001011547.3	MANE Select	c.260A>G	p.Asn87Ser	missense	Exon 3 of 14	NP_001011547.2	Q2M3M2-1
	SLC5A9	NM_001135181.2		c.260A>G	p.Asn87Ser	missense	Exon 3 of 15	NP_001128653.1	Q2M3M2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC5A9	ENST00000438567.7	TSL:1 MANE Select	c.260A>G	p.Asn87Ser	missense	Exon 3 of 14	ENSP00000401730.2	Q2M3M2-1
	SLC5A9	ENST00000236495.9	TSL:1	c.260A>G	p.Asn87Ser	missense	Exon 3 of 15	ENSP00000236495.5	Q2M3M2-2
	SLC5A9	ENST00000533824.5	TSL:1	c.260A>G	p.Asn87Ser	missense	Exon 3 of 15	ENSP00000431900.1	Q2M3M2-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461552 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727074

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53210

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111916

Other (OTH) AF: 0.00 AC: 0 AN: 60380

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Uncertain	0.057	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.047	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Pathogenic	0.80	D
MutationAssessor	Benign	1.8	L
PhyloP100		7.3
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-4.0	D
REVEL	Pathogenic	0.74
Sift	Benign	0.098	T
Sift4G	Benign	0.093	T
Polyphen		0.70	P
Vest4		0.72
MutPred		0.57		Gain of disorder (P = 0.0407)
MVP		0.47
MPC		0.68
ClinPred		1.0	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.33
gMVP		0.93
Mutation Taster		=47/53	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs1644202382; hg19: chr1-48694547;