chr17-6686031-A-T

Variant names:

• chr17-6686031-A-T
• rs218689
• NM_177550.5:c.*176T>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.*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
• Publications: 6 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=-0.83).
• BP6: Variant 17-6686031-A-T is Benign according to our data. Variant chr17-6686031-A-T is described in ClinVar as Benign. ClinVar VariationId 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.

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.*176T>A		3_prime_UTR	Exon 12 of 12	NP_808218.1	Q86YT5-1
	SLC13A5	NM_001284509.2		c.*176T>A		3_prime_UTR	Exon 12 of 12	NP_001271438.1	Q86YT5-3
	SLC13A5	NM_001284510.2		c.*176T>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.*176T>A		3_prime_UTR	Exon 12 of 12	ENSP00000406220.2	Q86YT5-1
	SLC13A5	ENST00000898130.1		c.*176T>A		3_prime_UTR	Exon 12 of 12	ENSP00000568189.1
	SLC13A5	ENST00000293800.10	TSL:2	c.*176T>A		3_prime_UTR	Exon 12 of 12	ENSP00000293800.6	Q86YT5-3

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

African (AFR) AF: 0.457 AC: 8177 AN: 17896

American (AMR) AF: 0.107 AC: 3127 AN: 29316

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 2674 AN: 15702

East Asian (EAS) AF: 0.106 AC: 3702 AN: 34958

South Asian (SAS) AF: 0.228 AC: 13058 AN: 57326

European-Finnish (FIN) AF: 0.141 AC: 4830 AN: 34186

Middle Eastern (MID) AF: 0.168 AC: 405 AN: 2408

European-Non Finnish (NFE) AF: 0.179 AC: 86885 AN: 484156

Other (OTH) AF: 0.191 AC: 6580 AN: 34420

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

African (AFR) AF: 0.457 AC: 18928 AN: 41390

American (AMR) AF: 0.163 AC: 2500 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 562 AN: 3468

East Asian (EAS) AF: 0.0880 AC: 454 AN: 5158

South Asian (SAS) AF: 0.220 AC: 1056 AN: 4808

European-Finnish (FIN) AF: 0.131 AC: 1390 AN: 10588

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.181 AC: 12291 AN: 67966

Other (OTH) AF: 0.219 AC: 462 AN: 2110

Alfa AF: 0.221 Hom.: 606

Bravo AF: 0.257

Asia WGS AF: 0.182 AC: 635 AN: 3478

ClinVar

ClinVar submissions

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	-0.83
CADD	Benign	2.8
DANN	Benign	0.62
PhyloP100		-0.063
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs218689; hg19: chr17-6589350;