chr17-6685892-C-T

Position:

• chr17-6685892-C-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.*315G>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 0.00888 in 342,526 control chromosomes in the GnomAD database, including 88 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (78 hom., cov: 32)
  • Exomes 𝑓: 0.0029 (10 hom.)
• Consequence: SLC13A5 NM_177550.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.640

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=-0.9).
• BP6: Variant 17-6685892-C-T is Benign according to our data. Variant chr17-6685892-C-T is described in ClinVar as [Benign]. Clinvar id is 1291908.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC13A5	NM_177550.5	c.*315G>A		3_prime_UTR_variant	12/12	ENST00000433363.7
SLC13A5	NM_001143838.3	c.*315G>A		3_prime_UTR_variant	11/11
SLC13A5	NM_001284509.2	c.*315G>A		3_prime_UTR_variant	12/12
SLC13A5	NM_001284510.2	c.*315G>A		3_prime_UTR_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC13A5	ENST00000433363.7	c.*315G>A		3_prime_UTR_variant	12/12	1	NM_177550.5	P1
	ENST00000634558.1	n.511-3984C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0164 AC: 2495 AN: 152140 Hom.: 77 Cov.: 32

Gnomad AFR AF: 0.0563

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00602

Gnomad ASJ AF: 0.00691

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.00670

GnomAD4 exome AF: 0.00286 AC: 545 AN: 190268 Hom.: 10 Cov.: 0 AF XY: 0.00246 AC XY: 245 AN XY: 99402

Gnomad4 AFR exome AF: 0.0510

Gnomad4 AMR exome AF: 0.00450

Gnomad4 ASJ exome AF: 0.00764

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000611

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000358

Gnomad4 OTH exome AF: 0.00497

GnomAD4 genome AF: 0.0164 AC: 2495 AN: 152258 Hom.: 78 Cov.: 32 AF XY: 0.0161 AC XY: 1195 AN XY: 74450

Gnomad4 AFR AF: 0.0562

Gnomad4 AMR AF: 0.00601

Gnomad4 ASJ AF: 0.00691

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000830

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.000338

Gnomad4 OTH AF: 0.00663

Alfa AF: 0.00833 Hom.: 4

Bravo AF: 0.0181

Asia WGS AF: 0.00375 AC: 13 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	clinical testing	GeneDx	Jun 28, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.24
DANN	Benign	0.60
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: rs16956117; hg19: chr17-6589211;