12-101158308-C-A

Position:

• chr12-101158308-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_145913.5(SLC5A8):​c.1651G>T​(p.Asp551Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 27)
• Consequence: SLC5A8 NM_145913.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.80

Genes affected

SLC5A8 (HGNC:19119): (solute carrier family 5 member 8) SLC5A8 has been shown to transport iodide by a passive mechanism (Rodriguez et al., 2002 [PubMed 12107270]) and monocarboxylates and short-chain fatty acids by a sodium-coupled mechanism (Gopal et al., 2004 [PubMed 15322102]). In kidney, SLC5A8 functions as a high-affinity sodium-coupled lactate transporter involved in reabsorption of lactate and maintenance of blood lactate levels (Thangaraju et al., 2006 [PubMed 16873376]).[supplied by OMIM, Dec 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC5A8	NM_145913.5	c.1651G>T	p.Asp551Tyr	missense_variant	14/15	ENST00000536262.3	NP_666018.3
SLC5A8	XR_007063055.1	n.2165G>T		non_coding_transcript_exon_variant	15/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC5A8	ENST00000536262.3	c.1651G>T	p.Asp551Tyr	missense_variant	14/15	1	NM_145913.5	ENSP00000445340.2

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 27

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 09, 2024

The c.1651G>T (p.D551Y) alteration is located in exon 14 (coding exon 14) of the SLC5A8 gene. This alteration results from a G to T substitution at nucleotide position 1651, causing the aspartic acid (D) at amino acid position 551 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.071	D
BayesDel_noAF	Benign	-0.14
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.75	D
Eigen	Benign	-0.033
Eigen_PC	Benign	0.087
FATHMM_MKL	Uncertain	0.94	D
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.62	D
MetaSVM	Benign	-0.76	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.20
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.038	D
Polyphen		0.044	B
Vest4		0.65
MutPred		0.47		Gain of sheet (P = 0.0149);
MVP		0.39
MPC		0.22
ClinPred		0.95	D
GERP RS		5.7
Varity_R		0.26
gMVP		0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-101552086;