17-18971122-G-A

Variant names:

• chr17-18971122-G-A
• rs201487616
• NM_001042450.4:c.750G>A

Variant summary

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

The NM_001042450.4(SLC5A10):​c.750G>A​(p.Met250Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000471 in 1,613,992 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M250T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000046 (0 hom.)
• Consequence: SLC5A10 NM_001042450.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.77
• Publications: 2 publications found

Genes affected

SLC5A10 (HGNC:23155): (solute carrier family 5 member 10) This gene is a member of the sodium/glucose transporter family. Members of this family are sodium-dependent transporters and can be divided into two subfamilies based on sequence homology, one that co-transports sugars and the second that transports molecules such as ascorbate, choline, iodide, lipoate, monocaroboxylates, and pantothenate. The protein encoded by this gene has the highest affinity for mannose and has been reported to be most highly expressed in the kidney. This protein may function as a kidney-specific, sodium-dependent mannose and fructose co-transporter. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, Jul 2012]

FAM83G (HGNC:32554): (family with sequence similarity 83 member G) Predicted to enable protein kinase binding activity. Involved in BMP signaling pathway. Located in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042450.4. 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
	SLC5A10	NM_001042450.4	MANE Select	c.750G>A	p.Met250Ile	missense	Exon 8 of 15	NP_001035915.1	A0PJK1-1
	FAM83G	NM_001039999.3	MANE Select	c.*237C>T		3_prime_UTR	Exon 6 of 6	NP_001035088.2	A6ND36-1
	SLC5A10	NM_152351.6		c.750G>A	p.Met250Ile	missense	Exon 8 of 15	NP_689564.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC5A10	ENST00000395645.4	TSL:1 MANE Select	c.750G>A	p.Met250Ile	missense	Exon 8 of 15	ENSP00000379007.3	A0PJK1-1
	SLC5A10	ENST00000395643.6	TSL:1	c.669G>A	p.Met223Ile	missense	Exon 7 of 14	ENSP00000379005.2	A0PJK1-2
	SLC5A10	ENST00000317977.10	TSL:1	c.501G>A	p.Met167Ile	missense	Exon 7 of 15	ENSP00000324346.6	A0PJK1-3

Frequencies

GnomAD3 genomes AF: 0.0000591 AC: 9 AN: 152222 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000279 AC: 7 AN: 251160 AF XY: 0.0000442

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: 0.0000617

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000458 AC: 67 AN: 1461770 Hom.: 0 Cov.: 32 AF XY: 0.0000619 AC XY: 45 AN XY: 727184

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 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: 86258

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53302

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000567 AC: 63 AN: 1112008

Other (OTH) AF: 0.0000331 AC: 2 AN: 60394

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152222 Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5 AN XY: 74364

African (AFR) AF: 0.00 AC: 0 AN: 41466

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000124 Hom.: 0

Bravo AF: 0.0000416

ExAC AF: 0.0000412 AC: 5

EpiCase AF: 0.000218

EpiControl AF: 0.00

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	Pathogenic	0.64
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Pathogenic	0.28
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.039	T
Eigen	Uncertain	0.56
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.076	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Uncertain	0.23	D
MutationAssessor	Benign	1.8	L
PhyloP100		6.8
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.1	N
REVEL	Pathogenic	0.72
Sift	Uncertain	0.028	D
Sift4G	Uncertain	0.017	D
Polyphen		0.86	P
Vest4		0.60
MutPred		0.68		Loss of disorder (P = 0.0662)
MVP		0.88
MPC		0.84
ClinPred		0.34	T
GERP RS		6.0
Varity_R		0.55
gMVP		0.86
Mutation Taster		=26/74	disease causing

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

Other links and lift over

dbSNP: rs201487616; hg19: chr17-18874435;