rs978069519

Variant names:

• chr12-59774779-G-C
• rs978069519
• NM_001270623.2:c.484G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001270623.2(SLC16A7):​c.484G>C​(p.Ala162Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,684 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: SLC16A7 NM_001270623.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 10.0
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.484G>C	p.Ala162Pro	missense	Exon 5 of 6	NP_001257552.1	O60669
	SLC16A7	NM_001270622.2		c.484G>C	p.Ala162Pro	missense	Exon 5 of 6	NP_001257551.1	O60669
	SLC16A7	NM_004731.5		c.484G>C	p.Ala162Pro	missense	Exon 4 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.484G>C	p.Ala162Pro	missense	Exon 5 of 6	ENSP00000448071.1	O60669
	SLC16A7	ENST00000261187.8	TSL:1	c.484G>C	p.Ala162Pro	missense	Exon 4 of 5	ENSP00000261187.4	O60669
	SLC16A7	ENST00000552432.5	TSL:1	c.484G>C	p.Ala162Pro	missense	Exon 5 of 6	ENSP00000449547.1	O60669

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461684 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 727152

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111888

Other (OTH) AF: 0.00 AC: 0 AN: 60378

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

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	0.84
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.85
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.7	L
PhyloP100		10
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-3.8	D
REVEL	Uncertain	0.49
Sift	Benign	0.45	T
Sift4G	Benign	0.18	T
Polyphen		0.95	P
Vest4		0.87
MutPred		0.69		Gain of catalytic residue at A162 (P = 2e-04)
MVP		0.71
MPC		0.43
ClinPred		0.93	D
GERP RS		6.1
Varity_R		0.97
gMVP		0.89
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: rs978069519; hg19: chr12-60168560;