chr12-101187431-A-C

Position:

• chr12-101187431-A-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_145913.5(SLC5A8):​c.918T>G​(p.His306Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC5A8 NM_145913.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.181

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.052239746).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC5A8	NM_145913.5	c.918T>G	p.His306Gln	missense_variant	7/15	ENST00000536262.3	NP_666018.3
SLC5A8	XM_017018910.3	c.918T>G	p.His306Gln	missense_variant	7/12		XP_016874399.1
SLC5A8	XR_007063055.1	n.1308T>G		non_coding_transcript_exon_variant	7/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC5A8	ENST00000536262.3	c.918T>G	p.His306Gln	missense_variant	7/15	1	NM_145913.5	ENSP00000445340.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Aug 19, 2024

The c.918T>G (p.H306Q) alteration is located in exon 7 (coding exon 7) of the SLC5A8 gene. This alteration results from a T to G substitution at nucleotide position 918, causing the histidine (H) at amino acid position 306 to be replaced by a glutamine (Q). 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	0.096
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	13
DANN	Benign	0.93
DEOGEN2	Benign	0.062	T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.14	N
M_CAP	Benign	0.052	D
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	0.74	N
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.090	N
REVEL	Benign	0.069
Sift	Benign	0.23	T
Sift4G	Benign	0.47	T
Polyphen		0.0030	B
Vest4		0.24
MutPred		0.32		Loss of methylation at R304 (P = 0.1383);
MVP		0.12
MPC		0.11
ClinPred		0.084	T
GERP RS		1.5
Varity_R		0.093
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr12-101581209;