17-6685892-C-T

Variant names:

• chr17-6685892-C-T
• rs16956117
• NM_177550.5:c.*315G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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]

ENSG00000290366 (HGNC:):

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_177550.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC13A5	NM_177550.5	MANE Select	c.*315G>A		3_prime_UTR	Exon 12 of 12	NP_808218.1	Q86YT5-1
	SLC13A5	NM_001284509.2		c.*315G>A		3_prime_UTR	Exon 12 of 12	NP_001271438.1	Q86YT5-3
	SLC13A5	NM_001284510.2		c.*315G>A		3_prime_UTR	Exon 11 of 11	NP_001271439.1	Q86YT5-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC13A5	ENST00000433363.7	TSL:1 MANE Select	c.*315G>A		3_prime_UTR	Exon 12 of 12	ENSP00000406220.2	Q86YT5-1
	SLC13A5	ENST00000898130.1		c.*315G>A		3_prime_UTR	Exon 12 of 12	ENSP00000568189.1
	SLC13A5	ENST00000293800.10	TSL:2	c.*315G>A		3_prime_UTR	Exon 12 of 12	ENSP00000293800.6	Q86YT5-3

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

African (AFR) AF: 0.0510 AC: 344 AN: 6742

American (AMR) AF: 0.00450 AC: 48 AN: 10664

Ashkenazi Jewish (ASJ) AF: 0.00764 AC: 44 AN: 5758

East Asian (EAS) AF: 0.00 AC: 0 AN: 12092

South Asian (SAS) AF: 0.000611 AC: 14 AN: 22924

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8560

Middle Eastern (MID) AF: 0.00127 AC: 1 AN: 786

European-Non Finnish (NFE) AF: 0.000358 AC: 40 AN: 111880

Other (OTH) AF: 0.00497 AC: 54 AN: 10862

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

African (AFR) AF: 0.0562 AC: 2334 AN: 41542

American (AMR) AF: 0.00601 AC: 92 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00691 AC: 24 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000830 AC: 4 AN: 4822

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10618

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000338 AC: 23 AN: 68018

Other (OTH) AF: 0.00663 AC: 14 AN: 2112

Alfa AF: 0.00792 Hom.: 4

Bravo AF: 0.0181

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.24
DANN	Benign	0.60
PhyloP100		-0.64
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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: rs16956117; hg19: chr17-6589211;