rs77707755

Positions:

• chr12-100380969-T-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_139319.3(SLC17A8):​c.354+16T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00399 in 1,613,734 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0037 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0040 (14 hom.)
• Consequence: SLC17A8 NM_139319.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.594

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 12-100380969-T-C is Benign according to our data. Variant chr12-100380969-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 262468.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 560 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC17A8	NM_139319.3	c.354+16T>C		intron_variant		ENST00000323346.10
SLC17A8	NM_001145288.2	c.354+16T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC17A8	ENST00000323346.10	c.354+16T>C		intron_variant		1	NM_139319.3	P1
SLC17A8	ENST00000392989.3	c.354+16T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.00367 AC: 559 AN: 152170 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.00432

Gnomad AMI AF: 0.0165

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00264

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00410

Gnomad OTH AF: 0.00383

GnomAD3 exomes AF: 0.00306 AC: 767 AN: 251028 Hom.: 3 AF XY: 0.00301 AC XY: 408 AN XY: 135698

Gnomad AFR exome AF: 0.00468

Gnomad AMR exome AF: 0.00168

Gnomad ASJ exome AF: 0.00208

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00150

Gnomad FIN exome AF: 0.00305

Gnomad NFE exome AF: 0.00427

Gnomad OTH exome AF: 0.00261

GnomAD4 exome AF: 0.00402 AC: 5877 AN: 1461446 Hom.: 14 Cov.: 31 AF XY: 0.00388 AC XY: 2818 AN XY: 727060

Gnomad4 AFR exome AF: 0.00571

Gnomad4 AMR exome AF: 0.00208

Gnomad4 ASJ exome AF: 0.00199

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00119

Gnomad4 FIN exome AF: 0.00303

Gnomad4 NFE exome AF: 0.00452

Gnomad4 OTH exome AF: 0.00360

GnomAD4 genome AF: 0.00368 AC: 560 AN: 152288 Hom.: 1 Cov.: 31 AF XY: 0.00342 AC XY: 255 AN XY: 74464

Gnomad4 AFR AF: 0.00433

Gnomad4 AMR AF: 0.00183

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00264

Gnomad4 NFE AF: 0.00410

Gnomad4 OTH AF: 0.00379

Alfa AF: 0.00309 Hom.: 0

Bravo AF: 0.00411

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 20, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 28, 2020	- -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.014
DANN	Benign	0.36

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: rs77707755; hg19: chr12-100774747;