NM_001352248.3:c.876T>C

Variant names:

• chr16-24897979-T-C
• rs150065146
• NM_001352248.3:c.876T>C

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001352248.3(SLC5A11):​c.876T>C​(p.Ile292Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC5A11 NM_001352248.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.621
• Publications: 0 publications found

Genes affected

SLC5A11 (HGNC:23091): (solute carrier family 5 member 11) Cotransporters, such as SLC5A11, represent a major class of proteins that make use of ion gradients to drive active transport for the cellular accumulation of nutrients, neurotransmitters, osmolytes, and ions Roll et al. (2002) [PubMed 12039040].[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.251063).
• BP7: Synonymous conserved (PhyloP=-0.621 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001352248.3. 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
	SLC5A11	NM_001352248.3	MANE Select	c.876T>C	p.Ile292Ile	synonymous	Exon 11 of 17	NP_001339177.1	Q8WWX8-1
	SLC5A11	NM_001352245.2		c.670T>C	p.Cys224Arg	missense	Exon 10 of 16	NP_001339174.1
	SLC5A11	NM_001352246.2		c.670T>C	p.Cys224Arg	missense	Exon 10 of 16	NP_001339175.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC5A11	ENST00000424767.7	TSL:2 MANE Select	c.876T>C	p.Ile292Ile	synonymous	Exon 11 of 17	ENSP00000416782.3	Q8WWX8-1
	SLC5A11	ENST00000347898.7	TSL:1	c.876T>C	p.Ile292Ile	synonymous	Exon 10 of 16	ENSP00000289932.3	Q8WWX8-1
	SLC5A11	ENST00000565769.5	TSL:1	c.684T>C	p.Ile228Ile	synonymous	Exon 10 of 16	ENSP00000457179.1	Q8WWX8-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461724 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727168

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5728

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111946

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Uncertain	0.071	D
BayesDel_noAF	Benign	-0.14
CADD	Benign	5.9
DANN	Benign	0.77
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.17	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.97	T
PhyloP100		-0.62
PROVEAN	Benign	-0.79	N
REVEL	Benign	0.24
Sift	Benign	0.18	T
Sift4G	Benign	0.34	T
Vest4		0.37
MutPred		0.72		Gain of disorder (P = 0.0138)
MVP		0.37
ClinPred		0.051	T
GERP RS		-6.2

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: rs150065146; hg19: chr16-24909300;