rs148144074

Variant names:

• chr6-73593585-G-C
• rs148144074
• NM_012434.5:c.*1492C>G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS1

The NM_012434.5(SLC17A5):​c.*1492C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00249 in 152,298 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0025 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC17A5 NM_012434.5 3_prime_UTR
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: -0.117
• Publications: 0 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 6-73593585-G-C is Benign according to our data. Variant chr6-73593585-G-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 357903.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00249 (379/152298) while in subpopulation AFR AF = 0.00739 (307/41560). AF 95% confidence interval is 0.00671. There are 0 homozygotes in GnomAd4. There are 174 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

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.*1492C>G		3_prime_UTR	Exon 11 of 11	NP_036566.1	Q9NRA2-1
	SLC17A5	NM_001382633.1		c.*1476C>G		3_prime_UTR	Exon 12 of 12	NP_001369562.1
	SLC17A5	NM_001382631.1		c.*1492C>G		3_prime_UTR	Exon 12 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.*1492C>G		3_prime_UTR	Exon 11 of 11	ENSP00000348019.5	Q9NRA2-1
	SLC17A5	ENST00000957535.1		c.*1492C>G		3_prime_UTR	Exon 11 of 11	ENSP00000627594.1
	SLC17A5	ENST00000908538.1		c.*1492C>G		3_prime_UTR	Exon 10 of 10	ENSP00000578597.1

Frequencies

GnomAD3 genomes AF: 0.00248 AC: 378 AN: 152180 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00736

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.00621

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.00249 AC: 379 AN: 152298 Hom.: 0 Cov.: 32 AF XY: 0.00234 AC XY: 174 AN XY: 74472

African (AFR) AF: 0.00739 AC: 307 AN: 41560

American (AMR) AF: 0.00144 AC: 22 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00403 AC: 14 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000279 AC: 19 AN: 68018

Other (OTH) AF: 0.00614 AC: 13 AN: 2116

Alfa AF: 0.00215 Hom.: 0

Bravo AF: 0.00271

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	1	-	Salla disease (1)
-	-	1	Sialic acid storage disease, severe infantile type (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.61
DANN	Benign	0.49
PhyloP100		-0.12

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: rs148144074; hg19: chr6-74303308;