17-6686031-A-T

Position:

• chr17-6686031-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_177550.5(SLC13A5):​c.*176T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 862,352 control chromosomes in the GnomAD database, including 18,844 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (6041 hom., cov: 32)
  • Exomes 𝑓: 0.18 (12803 hom.)
• Consequence: SLC13A5 NM_177550.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0630

Genes affected

SLC13A5 (HGNC:23089): (solute carrier family 13 member 5) This gene encodes a protein belonging to the solute carrier family 13 group of proteins. This family member is a sodium-dependent citrate cotransporter that may regulate metabolic processes. Mutations in this gene cause early infantile epileptic encephalopathy 25. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2014]

(HGNC:):

C17orf100 (HGNC:34494): (chromosome 17 open reading frame 100)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 17-6686031-A-T is Benign according to our data. Variant chr17-6686031-A-T is described in ClinVar as [Benign]. Clinvar id is 1183752.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC13A5	NM_177550.5	c.*176T>A		3_prime_UTR_variant	12/12	ENST00000433363.7
SLC13A5	NM_001143838.3	c.*176T>A		3_prime_UTR_variant	11/11
SLC13A5	NM_001284509.2	c.*176T>A		3_prime_UTR_variant	12/12
SLC13A5	NM_001284510.2	c.*176T>A		3_prime_UTR_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC13A5	ENST00000433363.7	c.*176T>A		3_prime_UTR_variant	12/12	1	NM_177550.5	P1
	ENST00000634558.1	n.511-3845A>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37805 AN: 151866 Hom.: 6037 Cov.: 32

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.0890

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.219

GnomAD4 exome AF: 0.182 AC: 129438 AN: 710368 Hom.: 12803 Cov.: 9 AF XY: 0.183 AC XY: 67351 AN XY: 368646

Gnomad4 AFR exome AF: 0.457

Gnomad4 AMR exome AF: 0.107

Gnomad4 ASJ exome AF: 0.170

Gnomad4 EAS exome AF: 0.106

Gnomad4 SAS exome AF: 0.228

Gnomad4 FIN exome AF: 0.141

Gnomad4 NFE exome AF: 0.179

Gnomad4 OTH exome AF: 0.191

GnomAD4 genome AF: 0.249 AC: 37828 AN: 151984 Hom.: 6041 Cov.: 32 AF XY: 0.242 AC XY: 18015 AN XY: 74292

Gnomad4 AFR AF: 0.457

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.162

Gnomad4 EAS AF: 0.0880

Gnomad4 SAS AF: 0.220

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.219

Alfa AF: 0.221 Hom.: 606

Bravo AF: 0.257

Asia WGS AF: 0.182 AC: 635 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	Jun 14, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.8
DANN	Benign	0.62
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs218689; hg19: chr17-6589350;