17-82237422-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004207.4(SLC16A3):c.652C>A(p.Leu218Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,427,648 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 Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLC16A3 NM_004207.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.430

Genes affected

SLC16A3 (HGNC:10924): (solute carrier family 16 member 3) Lactic acid and pyruvate transport across plasma membranes is catalyzed by members of the proton-linked monocarboxylate transporter (MCT) family, which has been designated solute carrier family-16. Each MCT appears to have slightly different substrate and inhibitor specificities and transport kinetics, which are related to the metabolic requirements of the tissues in which it is found. The MCTs, which include MCT1 (SLC16A1; MIM 600682) and MCT2 (SLC16A7; MIM 603654), are characterized by 12 predicted transmembrane domains (Price et al., 1998 [PubMed 9425115]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3982117).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC16A3	NM_004207.4	c.652C>A	p.Leu218Ile	missense_variant	4/5	ENST00000582743.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC16A3	ENST00000582743.6	c.652C>A	p.Leu218Ile	missense_variant	4/5	1	NM_004207.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000523 AC: 1 AN: 191270 Hom.: 0 AF XY: 0.00000950 AC XY: 1 AN XY: 105276

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000340

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1427648 Hom.: 0 Cov.: 31 AF XY: 0.00000141 AC XY: 1 AN XY: 708154

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000495

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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

Jul 25, 2023

The c.652C>A (p.L218I) alteration is located in exon 4 (coding exon 3) of the SLC16A3 gene. This alteration results from a C to A substitution at nucleotide position 652, causing the leucine (L) at amino acid position 218 to be replaced by an isoleucine (I). 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	0.23
BayesDel_addAF	Uncertain	0.060	T
BayesDel_noAF	Benign	-0.15
Cadd	Benign	21
Dann	Benign	0.93
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.81	T;T;T;.;T;T;.;.;.;T;.;T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.40	T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.56	T
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.70	T
Sift4G	Uncertain	0.059	T;T;T;T;T;T;T;T;T;T;T;D
Polyphen		1.0	.;D;.;D;.;.;D;D;D;.;D;.
Vest4		0.46, 0.46, 0.49, 0.43
MutPred		0.47		Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);.;Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);.;
MVP		0.82
MPC		0.99
ClinPred		0.68	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.18
gMVP		0.47

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

Publications

LitVar

Other links and lift over

dbSNP: rs1352991767; hg19: chr17-80195298;