NM_001270623.2:c.256C>T

Variant names:

• chr12-59771257-C-T
• rs558522051
• NM_001270623.2:c.256C>T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001270623.2(SLC16A7):​c.256C>T​(p.Arg86Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000149 in 1,613,098 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R86Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: SLC16A7 NM_001270623.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.96
• Publications: 1 publications found

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

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.942

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001270623.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC16A7	NM_001270623.2	MANE Select	c.256C>T	p.Arg86Trp	missense	Exon 4 of 6	NP_001257552.1	O60669
	SLC16A7	NM_001270622.2		c.256C>T	p.Arg86Trp	missense	Exon 4 of 6	NP_001257551.1	O60669
	SLC16A7	NM_004731.5		c.256C>T	p.Arg86Trp	missense	Exon 3 of 5	NP_004722.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC16A7	ENST00000547379.6	TSL:1 MANE Select	c.256C>T	p.Arg86Trp	missense	Exon 4 of 6	ENSP00000448071.1	O60669
	SLC16A7	ENST00000261187.8	TSL:1	c.256C>T	p.Arg86Trp	missense	Exon 3 of 5	ENSP00000261187.4	O60669
	SLC16A7	ENST00000552432.5	TSL:1	c.256C>T	p.Arg86Trp	missense	Exon 4 of 6	ENSP00000449547.1	O60669

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 152078 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000160 AC: 4 AN: 250212 AF XY: 0.0000222

Gnomad AFR exome AF: 0.0000618

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000546

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000151 AC: 22 AN: 1460902 Hom.: 0 Cov.: 30 AF XY: 0.0000179 AC XY: 13 AN XY: 726762

African (AFR) AF: 0.00 AC: 0 AN: 33418

American (AMR) AF: 0.00 AC: 0 AN: 44618

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.0000505 AC: 2 AN: 39622

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86184

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.0000162 AC: 18 AN: 1111442

Other (OTH) AF: 0.0000166 AC: 1 AN: 60352

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152196 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74410

African (AFR) AF: 0.0000241 AC: 1 AN: 41534

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68002

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.0000247 AC: 3

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.0000546

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Pathogenic	0.30
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.68	D
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Pathogenic	1.0	D
M_CAP	Uncertain	0.16	D
MetaRNN	Pathogenic	0.94	D
MetaSVM	Uncertain	0.43	D
MutationAssessor	Pathogenic	3.7	H
PhyloP100		5.0
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-7.0	D
REVEL	Pathogenic	0.72
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.94
MutPred		0.79		Gain of catalytic residue at A91 (P = 0)
MVP		0.96
MPC		0.39
ClinPred		1.0	D
GERP RS		5.9
Varity_R		0.82
gMVP		0.95
Mutation Taster		=14/86	disease causing

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

Other links and lift over

dbSNP: rs558522051; hg19: chr12-60165038;