12-59771302-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001270623.2(SLC16A7):c.301G>T(p.Val101Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,990 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SLC16A7 NM_001270623.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.55

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15633628).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC16A7	NM_001270623.2	c.301G>T	p.Val101Leu	missense_variant	4/6	ENST00000547379.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC16A7	ENST00000547379.6	c.301G>T	p.Val101Leu	missense_variant	4/6	1	NM_001270623.2	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250568 Hom.: 0 AF XY: 0.00000739 AC XY: 1 AN XY: 135408

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460990 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 726784

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

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

May 17, 2023

The c.301G>T (p.V101L) alteration is located in exon 3 (coding exon 2) of the SLC16A7 gene. This alteration results from a G to T substitution at nucleotide position 301, causing the valine (V) at amino acid position 101 to be replaced by a leucine (L). 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	0.12
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
Cadd	Benign	12
Dann	Benign	0.93
DEOGEN2	Benign	0.18	T;T;T;T;T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.77
FATHMM_MKL	Uncertain	0.85	D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.16	T;T;T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.6	L;L;L;.;L
MutationTaster	Benign	0.75	N;N;N;N;N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.5	N;N;N;N;N
REVEL	Benign	0.048
Sift	Uncertain	0.0070	D;D;D;D;D
Sift4G	Benign	0.30	T;T;T;T;T
Polyphen		0.0050	B;B;B;.;B
Vest4		0.24
MutPred		0.39		Gain of catalytic residue at L98 (P = 2e-04);Gain of catalytic residue at L98 (P = 2e-04);Gain of catalytic residue at L98 (P = 2e-04);Gain of catalytic residue at L98 (P = 2e-04);Gain of catalytic residue at L98 (P = 2e-04);
MVP		0.22
MPC		0.066
ClinPred		0.14	T
GERP RS		-0.40
Varity_R		0.39
gMVP		0.33

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: rs757021877; hg19: chr12-60165083;