12-59774663-G-A

Variant names:

• chr12-59774663-G-A
• rs778214706
• NM_001270623.2:c.368G>A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001270623.2(SLC16A7):​c.368G>A​(p.Gly123Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,427,244 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLC16A7 NM_001270623.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 10.0

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.955

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC16A7	NM_001270623.2	c.368G>A	p.Gly123Asp	missense_variant	Exon 5 of 6	ENST00000547379.6	NP_001257552.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC16A7	ENST00000547379.6	c.368G>A	p.Gly123Asp	missense_variant	Exon 5 of 6	1	NM_001270623.2	ENSP00000448071.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1427244 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 707674

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: 0.00000182

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000195 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.24
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.72	D;D;D;D;D;.
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.98
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	.;.;.;D;D;D
M_CAP	Benign	0.058	D
MetaRNN	Pathogenic	0.95	D;D;D;D;D;D
MetaSVM	Uncertain	0.076	D
MutationAssessor	Pathogenic	3.7	H;H;H;.;H;.
PrimateAI	Pathogenic	0.80	T
PROVEAN	Pathogenic	-6.4	D;D;D;D;D;D
REVEL	Pathogenic	0.69
Sift	Pathogenic	0.0	D;D;D;D;D;D
Sift4G	Uncertain	0.0020	D;D;D;D;D;D
Polyphen		1.0	D;D;D;.;D;.
Vest4		0.98
MutPred		0.82		Gain of catalytic residue at T120 (P = 0);Gain of catalytic residue at T120 (P = 0);Gain of catalytic residue at T120 (P = 0);Gain of catalytic residue at T120 (P = 0);Gain of catalytic residue at T120 (P = 0);.;
MVP		0.92
MPC		0.43
ClinPred		1.0	D
GERP RS		6.1
Varity_R		0.99
gMVP		0.98

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: rs778214706; hg19: chr12-60168444;