12-59774848-C-T

Variant names:

• chr12-59774848-C-T
• rs1420602142
• NM_001270623.2:c.553C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001270623.2(SLC16A7):​c.553C>T​(p.Leu185Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,660 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: SLC16A7 NM_001270623.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.768
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13609967).
• BP6: Variant 12-59774848-C-T is Benign according to our data. Variant chr12-59774848-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3442818.Status of the report is criteria_provided_single_submitter, 1 stars.

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.553C>T	p.Leu185Phe	missense	Exon 5 of 6	NP_001257552.1	O60669
	SLC16A7	NM_001270622.2		c.553C>T	p.Leu185Phe	missense	Exon 5 of 6	NP_001257551.1	O60669
	SLC16A7	NM_004731.5		c.553C>T	p.Leu185Phe	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.553C>T	p.Leu185Phe	missense	Exon 5 of 6	ENSP00000448071.1	O60669
	SLC16A7	ENST00000261187.8	TSL:1	c.553C>T	p.Leu185Phe	missense	Exon 4 of 5	ENSP00000261187.4	O60669
	SLC16A7	ENST00000552432.5	TSL:1	c.553C>T	p.Leu185Phe	missense	Exon 5 of 6	ENSP00000449547.1	O60669

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461660 Hom.: 0 Cov.: 33 AF XY: 0.00000688 AC XY: 5 AN XY: 727122

African (AFR) AF: 0.00 AC: 0 AN: 33452

American (AMR) AF: 0.00 AC: 0 AN: 44690

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000809 AC: 9 AN: 1111936

Other (OTH) AF: 0.00 AC: 0 AN: 60370

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

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	Benign	0.12
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	6.7
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.42	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.65	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.77
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.10
Sift	Benign	0.15	T
Sift4G	Uncertain	0.055	T
Polyphen		0.012	B
Vest4		0.27
MutPred		0.53		Gain of catalytic residue at S183 (P = 0)
MVP		0.28
MPC		0.078
ClinPred		0.16	T
GERP RS		-0.86
Varity_R		0.59
gMVP		0.66
Mutation Taster		=69/31	polymorphism

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: rs1420602142; hg19: chr12-60168629;