17-6686176-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_177550.5(SLC13A5):c.*31T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00594 in 1,613,602 control chromosomes in the GnomAD database, including 429 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.030 (213 hom., cov: 32)
  • Exomes 𝑓: 0.0035 (216 hom.)
• Consequence: SLC13A5 NM_177550.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.16

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 17-6686176-A-G is Benign according to our data. Variant chr17-6686176-A-G is described in ClinVar as [Benign]. Clinvar id is 1230912.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0983 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC13A5	NM_177550.5	c.*31T>C		3_prime_UTR_variant	12/12	ENST00000433363.7
SLC13A5	NM_001143838.3	c.*31T>C		3_prime_UTR_variant	11/11
SLC13A5	NM_001284509.2	c.*31T>C		3_prime_UTR_variant	12/12
SLC13A5	NM_001284510.2	c.*31T>C		3_prime_UTR_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC13A5	ENST00000433363.7	c.*31T>C		3_prime_UTR_variant	12/12	1	NM_177550.5	P1
	ENST00000634558.1	n.511-3700A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0296 AC: 4501 AN: 152072 Hom.: 211 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0128

Gnomad ASJ AF: 0.00116

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.000823

Gnomad OTH AF: 0.0263

GnomAD3 exomes AF: 0.00840 AC: 2110 AN: 251214 Hom.: 70 AF XY: 0.00619 AC XY: 840 AN XY: 135764

Gnomad AFR exome AF: 0.104

Gnomad AMR exome AF: 0.00782

Gnomad ASJ exome AF: 0.00179

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000783

Gnomad OTH exome AF: 0.00587

GnomAD4 exome AF: 0.00348 AC: 5083 AN: 1461412 Hom.: 216 Cov.: 31 AF XY: 0.00295 AC XY: 2148 AN XY: 727012

Gnomad4 AFR exome AF: 0.106

Gnomad4 AMR exome AF: 0.00895

Gnomad4 ASJ exome AF: 0.00161

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000197

Gnomad4 FIN exome AF: 0.0000562

Gnomad4 NFE exome AF: 0.000535

Gnomad4 OTH exome AF: 0.00736

GnomAD4 genome AF: 0.0296 AC: 4505 AN: 152190 Hom.: 213 Cov.: 32 AF XY: 0.0287 AC XY: 2137 AN XY: 74430

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.0128

Gnomad4 ASJ AF: 0.00116

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000824

Gnomad4 OTH AF: 0.0260

Alfa AF: 0.00848 Hom.: 53

Bravo AF: 0.0341

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 25, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	1.4
Dann	Benign	0.76
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: rs16956120; hg19: chr17-6589495;