chr12-59775099-G-C

Position:

• chr12-59775099-G-C

Variant summary

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

The NM_001270623.2(SLC16A7):​c.804G>C​(p.Leu268Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC16A7 NM_001270623.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.60

Genes affected

SLC16A7 (HGNC:10928): (solute carrier family 16 member 7) This gene is a member of the monocarboxylate transporter family. Members in this family transport metabolites, such as lactate, pyruvate, and ketone bodies. The protein encoded by this gene catalyzes the proton-linked transport of monocarboxylates and has the highest affinity for pyruvate. This protein has been reported to be more highly expressed in prostate and colorectal cancer specimens when compared to control specimens. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2012]

SLC16A7 (HGNC:):

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
SLC16A7	NM_001270623.2	c.804G>C	p.Leu268Phe	missense_variant	5/6	ENST00000547379.6	NP_001257552.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC16A7	ENST00000547379.6	c.804G>C	p.Leu268Phe	missense_variant	5/6	1	NM_001270623.2	ENSP00000448071.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

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

Sep 10, 2024

The c.804G>C (p.L268F) alteration is located in exon 4 (coding exon 3) of the SLC16A7 gene. This alteration results from a G to C substitution at nucleotide position 804, causing the leucine (L) at amino acid position 268 to be replaced by a phenylalanine (F). 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	Pathogenic	0.89
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.45	T;T;T;T;T
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.87	.;.;.;D;D
M_CAP	Benign	0.040	D
MetaRNN	Uncertain	0.71	D;D;D;D;D
MetaSVM	Uncertain	0.099	D
MutationAssessor	Pathogenic	3.6	H;H;H;.;H
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-3.6	D;D;D;D;D
REVEL	Uncertain	0.42
Sift	Uncertain	0.0020	D;D;D;D;D
Sift4G	Uncertain	0.0030	D;D;D;D;D
Polyphen		1.0	D;D;D;.;D
Vest4		0.78
MutPred		0.57		Gain of catalytic residue at A269 (P = 0);Gain of catalytic residue at A269 (P = 0);Gain of catalytic residue at A269 (P = 0);Gain of catalytic residue at A269 (P = 0);Gain of catalytic residue at A269 (P = 0);
MVP		0.78
MPC		0.40
ClinPred		0.99	D
GERP RS		5.8
Varity_R		0.90
gMVP		0.82

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-60168880;