6-73594106-C-T

Variant names:

• chr6-73594106-C-T
• rs670248
• NM_012434.5:c.*971G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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: G2P, Orphanet, Genomics England PanelApp, Myriad Women’s Health
• free sialic acid storage disease, infantile form

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SLC17A5	NM_012434.5	c.*971G>A		3_prime_UTR_variant	Exon 11 of 11	ENST00000355773.6	NP_036566.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC17A5	ENST00000355773.6	c.*971G>A		3_prime_UTR_variant	Exon 11 of 11	1	NM_012434.5	ENSP00000348019.5

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.167 AC: 3 AN: 18

Other (OTH) AF: 0.00 AC: 0 AN: 2

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

African (AFR) AF: 0.473 AC: 19515 AN: 41254

American (AMR) AF: 0.289 AC: 4386 AN: 15180

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 1390 AN: 3464

East Asian (EAS) AF: 0.0868 AC: 449 AN: 5170

South Asian (SAS) AF: 0.251 AC: 1205 AN: 4804

European-Finnish (FIN) AF: 0.361 AC: 3759 AN: 10408

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.373 AC: 25278 AN: 67816

Other (OTH) AF: 0.360 AC: 754 AN: 2096

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

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.39
DANN	Benign	0.58
PhyloP100		-2.3
Mutation Taster		=100/0	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: rs670248; hg19: chr6-74303829;