12-100380677-C-A

Position:

• chr12-100380677-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Moderate BP6_Very_Strong BS2

The NM_139319.3(SLC17A8):​c.102-24C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00518 in 1,612,640 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0037 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0053 (27 hom.)
• Consequence: SLC17A8 NM_139319.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.184

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 12-100380677-C-A is Benign according to our data. Variant chr12-100380677-C-A is described in ClinVar as [Benign]. Clinvar id is 1265235.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 565 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC17A8	NM_139319.3	c.102-24C>A		intron_variant		ENST00000323346.10
SLC17A8	NM_001145288.2	c.102-24C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC17A8	ENST00000323346.10	c.102-24C>A		intron_variant		1	NM_139319.3	P1
SLC17A8	ENST00000392989.3	c.102-24C>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.00374 AC: 566 AN: 151162 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.00114

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00238

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00125

Gnomad FIN AF: 0.00222

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00653

Gnomad OTH AF: 0.00145

GnomAD3 exomes AF: 0.00372 AC: 925 AN: 248486 Hom.: 4 AF XY: 0.00355 AC XY: 479 AN XY: 134828

Gnomad AFR exome AF: 0.000902

Gnomad AMR exome AF: 0.000984

Gnomad ASJ exome AF: 0.00219

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00108

Gnomad FIN exome AF: 0.00305

Gnomad NFE exome AF: 0.00659

Gnomad OTH exome AF: 0.00329

GnomAD4 exome AF: 0.00533 AC: 7782 AN: 1461364 Hom.: 27 Cov.: 31 AF XY: 0.00526 AC XY: 3826 AN XY: 727010

Gnomad4 AFR exome AF: 0.000598

Gnomad4 AMR exome AF: 0.000917

Gnomad4 ASJ exome AF: 0.00180

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00118

Gnomad4 FIN exome AF: 0.00316

Gnomad4 NFE exome AF: 0.00645

Gnomad4 OTH exome AF: 0.00338

GnomAD4 genome AF: 0.00373 AC: 565 AN: 151276 Hom.: 1 Cov.: 31 AF XY: 0.00389 AC XY: 287 AN XY: 73858

Gnomad4 AFR AF: 0.00112

Gnomad4 AMR AF: 0.00237

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00125

Gnomad4 FIN AF: 0.00222

Gnomad4 NFE AF: 0.00653

Gnomad4 OTH AF: 0.00143

Alfa AF: 0.00499 Hom.: 0

Bravo AF: 0.00349

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 03, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	12
DANN	Benign	0.75

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: rs148710845; hg19: chr12-100774455;