rs472294

Variant names:

• chr6-73644452-C-T
• rs472294
• NM_012434.5:c.246G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-73644452-C-T
• chr6-73644452-C-A
• chr6-73644452-C-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_012434.5(SLC17A5):​c.246G>A​(p.Ala82Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.082 in 1,613,430 control chromosomes in the GnomAD database, including 6,490 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1063 hom., cov: 33)
  • Exomes 𝑓: 0.079 (5427 hom.)
• Consequence: SLC17A5 NM_012434.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:12
• Conservation: PhyloP100: 0.753
• Publications: 20 publications found

Genes affected

SLC17A5 (HGNC:10933): (solute carrier family 17 member 5) This gene encodes a membrane transporter that exports free sialic acids that have been cleaved off of cell surface lipids and proteins from lysosomes. Mutations in this gene cause sialic acid storage diseases, including infantile sialic acid storage disorder and and Salla disease, an adult form. [provided by RefSeq, Jul 2008]

SLC17A5 Gene-Disease associations (from GenCC):

• free sialic acid storage disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Salla disease

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Myriad Women’s Health, G2P, PanelApp Australia, Orphanet, Genomics England PanelApp
• free sialic acid storage disease, infantile form

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, PanelApp Australia, Orphanet
• intermediate severe Salla disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 6-73644452-C-T is Benign according to our data. Variant chr6-73644452-C-T is described in ClinVar as Benign. ClinVar VariationId is 130316.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.753 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012434.5. 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
	SLC17A5	NM_012434.5	MANE Select	c.246G>A	p.Ala82Ala	synonymous	Exon 2 of 11	NP_036566.1	Q9NRA2-1
	SLC17A5	NM_001382633.1		c.246G>A	p.Ala82Ala	synonymous	Exon 2 of 12	NP_001369562.1
	SLC17A5	NM_001382631.1		c.267G>A	p.Ala89Ala	synonymous	Exon 3 of 12	NP_001369560.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC17A5	ENST00000355773.6	TSL:1 MANE Select	c.246G>A	p.Ala82Ala	synonymous	Exon 2 of 11	ENSP00000348019.5	Q9NRA2-1
	SLC17A5	ENST00000957536.1		c.246G>A	p.Ala82Ala	synonymous	Exon 2 of 12	ENSP00000627595.1
	SLC17A5	ENST00000957535.1		c.246G>A	p.Ala82Ala	synonymous	Exon 2 of 11	ENSP00000627594.1

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16303 AN: 152026 Hom.: 1062 Cov.: 33

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.0959

Gnomad FIN AF: 0.0484

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.0730

Gnomad OTH AF: 0.136

GnomAD2 exomes AF: 0.0988 AC: 24837 AN: 251362 AF XY: 0.0962

Gnomad AFR exome AF: 0.150

Gnomad AMR exome AF: 0.131

Gnomad ASJ exome AF: 0.155

Gnomad EAS exome AF: 0.170

Gnomad FIN exome AF: 0.0488

Gnomad NFE exome AF: 0.0732

Gnomad OTH exome AF: 0.114

GnomAD4 exome AF: 0.0793 AC: 115919 AN: 1461286 Hom.: 5427 Cov.: 32 AF XY: 0.0798 AC XY: 58003 AN XY: 727000

African (AFR) AF: 0.156 AC: 5219 AN: 33458

American (AMR) AF: 0.132 AC: 5922 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 4101 AN: 26120

East Asian (EAS) AF: 0.176 AC: 6980 AN: 39674

South Asian (SAS) AF: 0.103 AC: 8908 AN: 86228

European-Finnish (FIN) AF: 0.0504 AC: 2690 AN: 53410

Middle Eastern (MID) AF: 0.180 AC: 1039 AN: 5766

European-Non Finnish (NFE) AF: 0.0676 AC: 75137 AN: 1111540

Other (OTH) AF: 0.0981 AC: 5923 AN: 60372

GnomAD4 genome AF: 0.107 AC: 16324 AN: 152144 Hom.: 1063 Cov.: 33 AF XY: 0.107 AC XY: 7931 AN XY: 74384

African (AFR) AF: 0.154 AC: 6393 AN: 41478

American (AMR) AF: 0.143 AC: 2191 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 544 AN: 3470

East Asian (EAS) AF: 0.171 AC: 884 AN: 5174

South Asian (SAS) AF: 0.0966 AC: 466 AN: 4824

European-Finnish (FIN) AF: 0.0484 AC: 513 AN: 10596

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.0730 AC: 4965 AN: 68010

Other (OTH) AF: 0.135 AC: 285 AN: 2106

Alfa AF: 0.0898 Hom.: 2497

Bravo AF: 0.117

Asia WGS AF: 0.143 AC: 497 AN: 3478

EpiCase AF: 0.0832

EpiControl AF: 0.0836

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	4	Salla disease (4)
-	-	2	not provided (2)
-	-	2	Sialic acid storage disease, severe infantile type (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	13
DANN	Benign	0.48
PhyloP100		0.75
Mutation Taster		=100/0	polymorphism (auto)

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: rs472294; hg19: chr6-74354175;