12-59779575-A-T

Variant names:

• chr12-59779575-A-T
• rs3763980
• NM_001270623.2:c.1333A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001270623.2(SLC16A7):​c.1333A>T​(p.Thr445Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 1,610,890 control chromosomes in the GnomAD database, including 49,172 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.24 (4361 hom., cov: 32)
  • Exomes 𝑓: 0.25 (44811 hom.)
• Consequence: SLC16A7 NM_001270623.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.962
• Publications: 39 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008133441).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC16A7	NM_001270623.2	MANE Select	c.1333A>T	p.Thr445Ser	missense	Exon 6 of 6	NP_001257552.1
	SLC16A7	NM_001270622.2		c.1333A>T	p.Thr445Ser	missense	Exon 6 of 6	NP_001257551.1
	SLC16A7	NM_004731.5		c.1333A>T	p.Thr445Ser	missense	Exon 5 of 5	NP_004722.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC16A7	ENST00000547379.6	TSL:1 MANE Select	c.1333A>T	p.Thr445Ser	missense	Exon 6 of 6	ENSP00000448071.1
	SLC16A7	ENST00000261187.8	TSL:1	c.1333A>T	p.Thr445Ser	missense	Exon 5 of 5	ENSP00000261187.4
	SLC16A7	ENST00000552432.5	TSL:1	c.1333A>T	p.Thr445Ser	missense	Exon 6 of 6	ENSP00000449547.1

Frequencies

GnomAD3 genomes AF: 0.237 AC: 35989 AN: 151888 Hom.: 4357 Cov.: 32

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.309

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.256

GnomAD2 exomes AF: 0.229 AC: 56944 AN: 248474 AF XY: 0.233

Gnomad AFR exome AF: 0.211

Gnomad AMR exome AF: 0.136

Gnomad ASJ exome AF: 0.231

Gnomad EAS exome AF: 0.306

Gnomad FIN exome AF: 0.234

Gnomad NFE exome AF: 0.247

Gnomad OTH exome AF: 0.246

GnomAD4 exome AF: 0.246 AC: 358398 AN: 1458882 Hom.: 44811 Cov.: 31 AF XY: 0.246 AC XY: 178733 AN XY: 725716

African (AFR) AF: 0.218 AC: 7288 AN: 33394

American (AMR) AF: 0.144 AC: 6383 AN: 44468

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 6121 AN: 26102

East Asian (EAS) AF: 0.321 AC: 12716 AN: 39586

South Asian (SAS) AF: 0.231 AC: 19935 AN: 86158

European-Finnish (FIN) AF: 0.235 AC: 12508 AN: 53336

Middle Eastern (MID) AF: 0.229 AC: 1318 AN: 5766

European-Non Finnish (NFE) AF: 0.250 AC: 277504 AN: 1109838

Other (OTH) AF: 0.243 AC: 14625 AN: 60234

GnomAD4 genome AF: 0.237 AC: 36006 AN: 152008 Hom.: 4361 Cov.: 32 AF XY: 0.238 AC XY: 17658 AN XY: 74322

African (AFR) AF: 0.219 AC: 9072 AN: 41466

American (AMR) AF: 0.203 AC: 3097 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 778 AN: 3472

East Asian (EAS) AF: 0.309 AC: 1593 AN: 5162

South Asian (SAS) AF: 0.237 AC: 1140 AN: 4820

European-Finnish (FIN) AF: 0.237 AC: 2508 AN: 10582

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.249 AC: 16904 AN: 67960

Other (OTH) AF: 0.258 AC: 542 AN: 2104

Alfa AF: 0.246 Hom.: 3648

Bravo AF: 0.233

TwinsUK AF: 0.255 AC: 944

ALSPAC AF: 0.245 AC: 945

ESP6500AA AF: 0.212 AC: 934

ESP6500EA AF: 0.239 AC: 2055

ExAC AF: 0.231 AC: 28076

Asia WGS AF: 0.222 AC: 775 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.84	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.22
DANN	Benign	0.097
DEOGEN2	Benign	0.032	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.18	T
MetaRNN	Benign	0.0081	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-1.3	N
PhyloP100		0.96
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.41	N
REVEL	Benign	0.021
Sift	Benign	1.0	T
Sift4G	Benign	0.88	T
Polyphen		0.0	B
Vest4		0.035
MutPred		0.28		Gain of catalytic residue at R446 (P = 0.0416)
MPC		0.056
ClinPred		0.00015	T
GERP RS		-2.5
Varity_R		0.064
gMVP		0.22
Mutation Taster		=98/2	polymorphism (auto)

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: rs3763980; hg19: chr12-60173356; COSMIC: COSV53895053; COSMIC: COSV53895053;