rs16883930

Variant names:

• chr6-73621896-C-T
• rs16883930
• NM_012434.5:c.886G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_012434.5(SLC17A5):​c.886G>A​(p.Val296Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0117 in 1,613,866 control chromosomes in the GnomAD database, including 463 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (57 hom., cov: 33)
  • Exomes 𝑓: 0.011 (406 hom.)
• Consequence: SLC17A5 NM_012434.5 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 5.70
• Publications: 15 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0022813678).
• BP6: Variant 6-73621896-C-T is Benign according to our data. Variant chr6-73621896-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 198552.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.102 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.886G>A	p.Val296Ile	missense	Exon 7 of 11	NP_036566.1	Q9NRA2-1
	SLC17A5	NM_001382633.1		c.886G>A	p.Val296Ile	missense	Exon 7 of 12	NP_001369562.1
	SLC17A5	NM_001382631.1		c.907G>A	p.Val303Ile	missense	Exon 8 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.886G>A	p.Val296Ile	missense	Exon 7 of 11	ENSP00000348019.5	Q9NRA2-1
	SLC17A5	ENST00000957536.1		c.1000G>A	p.Val334Ile	missense	Exon 8 of 12	ENSP00000627595.1
	SLC17A5	ENST00000957535.1		c.808G>A	p.Val270Ile	missense	Exon 7 of 11	ENSP00000627594.1

Frequencies

GnomAD3 genomes AF: 0.0150 AC: 2279 AN: 152146 Hom.: 57 Cov.: 33

Gnomad AFR AF: 0.00721

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0415

Gnomad ASJ AF: 0.0170

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.0176

Gnomad FIN AF: 0.0128

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.00628

Gnomad OTH AF: 0.0292

GnomAD2 exomes AF: 0.0236 AC: 5939 AN: 251438 AF XY: 0.0214

Gnomad AFR exome AF: 0.00615

Gnomad AMR exome AF: 0.0554

Gnomad ASJ exome AF: 0.0206

Gnomad EAS exome AF: 0.109

Gnomad FIN exome AF: 0.0131

Gnomad NFE exome AF: 0.00627

Gnomad OTH exome AF: 0.0254

GnomAD4 exome AF: 0.0114 AC: 16613 AN: 1461602 Hom.: 406 Cov.: 31 AF XY: 0.0112 AC XY: 8111 AN XY: 727126

African (AFR) AF: 0.00633 AC: 212 AN: 33474

American (AMR) AF: 0.0543 AC: 2429 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0218 AC: 569 AN: 26128

East Asian (EAS) AF: 0.0993 AC: 3939 AN: 39656

South Asian (SAS) AF: 0.0186 AC: 1608 AN: 86252

European-Finnish (FIN) AF: 0.0119 AC: 633 AN: 53416

Middle Eastern (MID) AF: 0.0397 AC: 229 AN: 5764

European-Non Finnish (NFE) AF: 0.00523 AC: 5815 AN: 1111814

Other (OTH) AF: 0.0195 AC: 1179 AN: 60376

GnomAD4 genome AF: 0.0150 AC: 2281 AN: 152264 Hom.: 57 Cov.: 33 AF XY: 0.0159 AC XY: 1180 AN XY: 74438

African (AFR) AF: 0.00719 AC: 299 AN: 41568

American (AMR) AF: 0.0416 AC: 635 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0170 AC: 59 AN: 3472

East Asian (EAS) AF: 0.109 AC: 565 AN: 5182

South Asian (SAS) AF: 0.0176 AC: 85 AN: 4830

European-Finnish (FIN) AF: 0.0128 AC: 136 AN: 10600

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.00628 AC: 427 AN: 68012

Other (OTH) AF: 0.0293 AC: 62 AN: 2114

Alfa AF: 0.0114 Hom.: 153

Bravo AF: 0.0176

TwinsUK AF: 0.00539 AC: 20

ALSPAC AF: 0.00467 AC: 18

ESP6500AA AF: 0.00590 AC: 26

ESP6500EA AF: 0.00709 AC: 61

ExAC AF: 0.0221 AC: 2682

Asia WGS AF: 0.0740 AC: 257 AN: 3478

EpiCase AF: 0.00747

EpiControl AF: 0.00747

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	3	Salla disease (3)
-	-	1	not provided (1)
-	-	1	Sialic acid storage disease, severe infantile type (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.17	T
Eigen	Benign	0.095
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.86	D
MetaRNN	Benign	0.0023	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.84	L
PhyloP100		5.7
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.41	N
REVEL	Benign	0.20
Sift	Benign	0.38	T
Sift4G	Benign	0.58	T
Polyphen		0.58	P
Vest4		0.14
MPC		0.16
ClinPred		0.017	T
GERP RS		5.9
Varity_R		0.13
gMVP		0.26
Mutation Taster		=84/16	polymorphism (auto)

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: rs16883930; hg19: chr6-74331619; COSMIC: COSV107451146; COSMIC: COSV107451146;