6-73594106-C-T

Position:

• chr6-73594106-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_012434.5(SLC17A5):​c.*971G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 151,412 control chromosomes in the GnomAD database, including 11,393 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.38 (11393 hom., cov: 29)
  • Exomes 𝑓: 0.18 (0 hom.)
• Consequence: SLC17A5 NM_012434.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -2.27

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 6-73594106-C-T is Benign according to our data. Variant chr6-73594106-C-T is described in ClinVar as [Benign]. Clinvar id is 357907.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC17A5	NM_012434.5	c.*971G>A		3_prime_UTR_variant	11/11	ENST00000355773.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC17A5	ENST00000355773.6	c.*971G>A		3_prime_UTR_variant	11/11	1	NM_012434.5	P1

Frequencies

GnomAD3 genomes AF: 0.377 AC: 57072 AN: 151272 Hom.: 11381 Cov.: 29

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.0870

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.373

Gnomad OTH AF: 0.364

GnomAD4 exome AF: 0.182 AC: 4 AN: 22 Hom.: 0 Cov.: 0 AF XY: 0.143 AC XY: 2 AN XY: 14

Gnomad4 ASJ exome AF: 0.500

Gnomad4 NFE exome AF: 0.167

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.377 AC: 57120 AN: 151390 Hom.: 11393 Cov.: 29 AF XY: 0.373 AC XY: 27566 AN XY: 73918

Gnomad4 AFR AF: 0.473

Gnomad4 AMR AF: 0.289

Gnomad4 ASJ AF: 0.401

Gnomad4 EAS AF: 0.0868

Gnomad4 SAS AF: 0.251

Gnomad4 FIN AF: 0.361

Gnomad4 NFE AF: 0.373

Gnomad4 OTH AF: 0.360

Alfa AF: 0.382 Hom.: 1451

Bravo AF: 0.375

Asia WGS AF: 0.179 AC: 625 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Sialic acid storage disease, severe infantile type Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Salla disease Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.39
DANN	Benign	0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs670248; hg19: chr6-74303829;