rs10860582

Variant names:

• chr12-100357174-T-C
• rs10860582
• NM_139319.3:c.-218T>C

Variant summary

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

The NM_139319.3(SLC17A8):​c.-218T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 511,460 control chromosomes in the GnomAD database, including 8,736 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2578 hom., cov: 32)
  • Exomes 𝑓: 0.17 (6158 hom.)
• Consequence: SLC17A8 NM_139319.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.117
• Publications: 5 publications found

Genes affected

SLC17A8 (HGNC:20151): (solute carrier family 17 member 8) This gene encodes a vesicular glutamate transporter. The encoded protein transports the neurotransmitter glutamate into synaptic vesicles before it is released into the synaptic cleft. Mutations in this gene are the cause of autosomal-dominant nonsyndromic type 25 deafness. Alternate splicing results in multiple transcript variants.[provided by RefSeq, May 2010]

SLC17A8 Gene-Disease associations (from GenCC):

• nonsyndromic genetic hearing loss

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• autosomal dominant nonsyndromic hearing loss 25

  Inheritance: AD, Unknown Classification: STRONG, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 12-100357174-T-C is Benign according to our data. Variant chr12-100357174-T-C is described in ClinVar as Benign. ClinVar VariationId is 306619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139319.3. 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
	SLC17A8	NM_139319.3	MANE Select	c.-218T>C		5_prime_UTR	Exon 1 of 12	NP_647480.1	Q8NDX2-1
	SLC17A8	NM_001145288.2		c.-218T>C		5_prime_UTR	Exon 1 of 11	NP_001138760.1	Q8NDX2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC17A8	ENST00000323346.10	TSL:1 MANE Select	c.-218T>C		5_prime_UTR	Exon 1 of 12	ENSP00000316909.4	Q8NDX2-1
	SLC17A8	ENST00000874772.1		c.-128-90T>C		intron	N/A	ENSP00000544831.1
	SLC17A8	ENST00000392989.3	TSL:1	c.-218T>C		upstream_gene	N/A	ENSP00000376715.3	Q8NDX2-2

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26785 AN: 151990 Hom.: 2575 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.00426

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.186

GnomAD4 exome AF: 0.173 AC: 61991 AN: 359352 Hom.: 6158 Cov.: 0 AF XY: 0.170 AC XY: 32892 AN XY: 193610

African (AFR) AF: 0.173 AC: 1758 AN: 10166

American (AMR) AF: 0.137 AC: 2314 AN: 16856

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 2331 AN: 10894

East Asian (EAS) AF: 0.00332 AC: 74 AN: 22260

South Asian (SAS) AF: 0.120 AC: 5408 AN: 44954

European-Finnish (FIN) AF: 0.135 AC: 2499 AN: 18560

Middle Eastern (MID) AF: 0.159 AC: 236 AN: 1488

European-Non Finnish (NFE) AF: 0.205 AC: 43872 AN: 214162

Other (OTH) AF: 0.175 AC: 3499 AN: 20012

GnomAD4 genome AF: 0.176 AC: 26810 AN: 152108 Hom.: 2578 Cov.: 32 AF XY: 0.170 AC XY: 12663 AN XY: 74370

African (AFR) AF: 0.166 AC: 6898 AN: 41502

American (AMR) AF: 0.165 AC: 2521 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 771 AN: 3468

East Asian (EAS) AF: 0.00427 AC: 22 AN: 5156

South Asian (SAS) AF: 0.112 AC: 540 AN: 4820

European-Finnish (FIN) AF: 0.128 AC: 1360 AN: 10586

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14069 AN: 67970

Other (OTH) AF: 0.189 AC: 399 AN: 2116

Alfa AF: 0.203 Hom.: 3262

Bravo AF: 0.178

Asia WGS AF: 0.0810 AC: 282 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Autosomal dominant nonsyndromic hearing loss 25 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.3
DANN	Benign	0.54
PhyloP100		-0.12
PromoterAI		0.0053	Neutral
Mutation Taster		=300/0	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: rs10860582; hg19: chr12-100750952;