rs943403

Variant names:

• chr12-100380391-A-G
• rs943403
• NM_139319.3:c.102-310A>G

Your query was ambiguous. Multiple possible variants found:

• chr12-100380391-A-G
• chr12-100380391-A-C
• chr12-100380391-A-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_139319.3(SLC17A8):​c.102-310A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 151,546 control chromosomes in the GnomAD database, including 32,876 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.64 (32876 hom., cov: 29)
• Consequence: SLC17A8 NM_139319.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.233
• Publications: 0 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 12-100380391-A-G is Benign according to our data. Variant chr12-100380391-A-G is described in ClinVar as Benign. ClinVar VariationId is 1225423.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 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.102-310A>G		intron	N/A	NP_647480.1	Q8NDX2-1
	SLC17A8	NM_001145288.2		c.102-310A>G		intron	N/A	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.102-310A>G		intron	N/A	ENSP00000316909.4	Q8NDX2-1
	SLC17A8	ENST00000392989.3	TSL:1	c.102-310A>G		intron	N/A	ENSP00000376715.3	Q8NDX2-2
	SLC17A8	ENST00000874772.1		c.102-310A>G		intron	N/A	ENSP00000544831.1

Frequencies

GnomAD3 genomes AF: 0.640 AC: 96897 AN: 151430 Hom.: 32837 Cov.: 29

Gnomad AFR AF: 0.828

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.671

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.707

Gnomad FIN AF: 0.593

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.622

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.640 AC: 96995 AN: 151546 Hom.: 32876 Cov.: 29 AF XY: 0.647 AC XY: 47867 AN XY: 74022

African (AFR) AF: 0.828 AC: 34212 AN: 41324

American (AMR) AF: 0.671 AC: 10213 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.529 AC: 1836 AN: 3470

East Asian (EAS) AF: 0.994 AC: 5121 AN: 5152

South Asian (SAS) AF: 0.706 AC: 3389 AN: 4800

European-Finnish (FIN) AF: 0.593 AC: 6180 AN: 10430

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.502 AC: 34087 AN: 67858

Other (OTH) AF: 0.622 AC: 1304 AN: 2098

Alfa AF: 0.479 Hom.: 2729

Bravo AF: 0.657

Asia WGS AF: 0.834 AC: 2899 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.74
PhyloP100		-0.23
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: rs943403; hg19: chr12-100774169;