chr12-100357451-A-T

Position:

• chr12-100357451-A-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2 BP4_Strong BP6_Moderate BP7 BS2

The NM_139319.3(SLC17A8):​c.60A>T​(p.Gly20=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,654 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: SLC17A8 NM_139319.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.590

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 -9 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 12-100357451-A-T is Benign according to our data. Variant chr12-100357451-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 2875508.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.59 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC17A8	NM_139319.3	c.60A>T	p.Gly20=	synonymous_variant	1/12	ENST00000323346.10	NP_647480.1
SLC17A8	NM_001145288.2	c.60A>T	p.Gly20=	synonymous_variant	1/11		NP_001138760.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC17A8	ENST00000323346.10	c.60A>T	p.Gly20=	synonymous_variant	1/12	1	NM_139319.3	ENSP00000316909	P1
SLC17A8	ENST00000392989.3	c.60A>T	p.Gly20=	synonymous_variant	1/11	1		ENSP00000376715

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461654 Hom.: 0 Cov.: 29 AF XY: 0.00000550 AC XY: 4 AN XY: 727156

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000450

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 13, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	8.7
DANN	Benign	0.70

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: rs1219817580; hg19: chr12-100751229;