12-59771332-C-G

Position:

• chr12-59771332-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001270623.2(SLC16A7):​c.331C>G​(p.Gln111Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC16A7 NM_001270623.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.118

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_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07659808).
• BP6: Variant 12-59771332-C-G is Benign according to our data. Variant chr12-59771332-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2289418.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC16A7	NM_001270623.2	c.331C>G	p.Gln111Glu	missense_variant	4/6	ENST00000547379.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC16A7	ENST00000547379.6	c.331C>G	p.Gln111Glu	missense_variant	4/6	1	NM_001270623.2	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 11, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.049
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.043
DANN	Benign	0.075
DEOGEN2	Benign	0.13	T;T;T;T;T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.55	.;.;.;T;T
M_CAP	Uncertain	0.087	D
MetaRNN	Benign	0.077	T;T;T;T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	-0.38	N;N;N;.;N
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.080	N;N;N;N;N
REVEL	Benign	0.11
Sift	Benign	0.95	T;T;T;T;T
Sift4G	Benign	0.99	T;T;T;T;T
Polyphen		0.0010	B;B;B;.;B
Vest4		0.29
MutPred		0.51		Gain of catalytic residue at S107 (P = 0);Gain of catalytic residue at S107 (P = 0);Gain of catalytic residue at S107 (P = 0);Gain of catalytic residue at S107 (P = 0);Gain of catalytic residue at S107 (P = 0);
MVP		0.34
MPC		0.066
ClinPred		0.016	T
GERP RS		-11
Varity_R		0.15
gMVP		0.61

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-60165113;