17-6687643-C-T

Variant names:

• chr17-6687643-C-T
• rs374067396
• NM_177550.5:c.1461G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_177550.5(SLC13A5):​c.1461G>A​(p.Pro487Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000828 in 1,606,580 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P487P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000085 (0 hom.)
• Consequence: SLC13A5 NM_177550.5 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.23
• Publications: 1 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 17-6687643-C-T is Benign according to our data. Variant chr17-6687643-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 383584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.23 with no splicing effect.

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.1461G>A	p.Pro487Pro	synonymous	Exon 11 of 12	NP_808218.1	Q86YT5-1
	SLC13A5	NM_001284509.2		c.1410G>A	p.Pro470Pro	synonymous	Exon 11 of 12	NP_001271438.1	Q86YT5-3
	SLC13A5	NM_001284510.2		c.1332G>A	p.Pro444Pro	synonymous	Exon 10 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.1461G>A	p.Pro487Pro	synonymous	Exon 11 of 12	ENSP00000406220.2	Q86YT5-1
	SLC13A5	ENST00000573648.5	TSL:1	c.1438-1305G>A		intron	N/A	ENSP00000459372.1	Q86YT5-2
	SLC13A5	ENST00000898130.1		c.1461G>A	p.Pro487Pro	synonymous	Exon 11 of 12	ENSP00000568189.1

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152162 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000860 AC: 21 AN: 244180 AF XY: 0.0000757

Gnomad AFR exome AF: 0.0000623

Gnomad AMR exome AF: 0.0000627

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000167

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000125

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000846 AC: 123 AN: 1454418 Hom.: 0 Cov.: 30 AF XY: 0.0000913 AC XY: 66 AN XY: 723100

African (AFR) AF: 0.0000302 AC: 1 AN: 33120

American (AMR) AF: 0.0000697 AC: 3 AN: 43062

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25986

East Asian (EAS) AF: 0.000127 AC: 5 AN: 39414

South Asian (SAS) AF: 0.00 AC: 0 AN: 84584

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53382

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5748

European-Non Finnish (NFE) AF: 0.0000992 AC: 110 AN: 1109050

Other (OTH) AF: 0.0000333 AC: 2 AN: 60072

GnomAD4 genome AF: 0.0000657 AC: 10 AN: 152162 Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6 AN XY: 74332

African (AFR) AF: 0.0000241 AC: 1 AN: 41428

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000112 Hom.: 0

Bravo AF: 0.0000453

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Developmental and epileptic encephalopathy, 25 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	7.2
DANN	Benign	0.77
PhyloP100		-4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs374067396; hg19: chr17-6590962; COSMIC: COSV53421687; COSMIC: COSV53421687;