rs10778050

Variant names:

• chr12-100375049-G-A
• rs10778050
• NM_139319.3:c.102-5652G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-100375049-G-A
• chr12-100375049-G-C
• chr12-100375049-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139319.3(SLC17A8):​c.102-5652G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 150,450 control chromosomes in the GnomAD database, including 22,733 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.54 (22733 hom., cov: 27)
• Consequence: SLC17A8 NM_139319.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.847 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC17A8	NM_139319.3	MANE Select	c.102-5652G>A		intron	N/A	NP_647480.1
	SLC17A8	NM_001145288.2		c.102-5652G>A		intron	N/A	NP_001138760.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC17A8	ENST00000323346.10	TSL:1 MANE Select	c.102-5652G>A		intron	N/A	ENSP00000316909.4
	SLC17A8	ENST00000392989.3	TSL:1	c.102-5652G>A		intron	N/A	ENSP00000376715.3

Frequencies

GnomAD3 genomes AF: 0.543 AC: 81577 AN: 150332 Hom.: 22721 Cov.: 27

Gnomad AFR AF: 0.561

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.621

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.868

Gnomad SAS AF: 0.699

Gnomad FIN AF: 0.534

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.541

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

GnomAD4 genome AF: 0.543 AC: 81633 AN: 150450 Hom.: 22733 Cov.: 27 AF XY: 0.550 AC XY: 40357 AN XY: 73372

African (AFR) AF: 0.560 AC: 22871 AN: 40810

American (AMR) AF: 0.622 AC: 9349 AN: 15042

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1745 AN: 3456

East Asian (EAS) AF: 0.868 AC: 4454 AN: 5130

South Asian (SAS) AF: 0.698 AC: 3272 AN: 4688

European-Finnish (FIN) AF: 0.534 AC: 5517 AN: 10322

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.483 AC: 32729 AN: 67722

Other (OTH) AF: 0.540 AC: 1124 AN: 2082

Alfa AF: 0.509 Hom.: 81138

Bravo AF: 0.551

Asia WGS AF: 0.753 AC: 2616 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.0
DANN	Benign	0.48
PhyloP100		1.1
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: rs10778050; hg19: chr12-100768827;