chr2-230046059-G-C

Variant names:

• chr2-230046059-G-C
• rs2077603558
• NM_152527.5:c.1067C>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_152527.5(SLC16A14):​c.1067C>G​(p.Thr356Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T356M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC16A14 NM_152527.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.60
• Publications: 0 publications found

Genes affected

SLC16A14 (HGNC:26417): (solute carrier family 16 member 14) Predicted to enable monocarboxylic acid transmembrane transporter activity. Predicted to be involved in monocarboxylic acid transport. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

LOC107985996 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.868

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC16A14	NM_152527.5	c.1067C>G	p.Thr356Arg	missense_variant	Exon 4 of 5	ENST00000295190.9	NP_689740.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC16A14	ENST00000295190.9	c.1067C>G	p.Thr356Arg	missense_variant	Exon 4 of 5	1	NM_152527.5	ENSP00000295190.4
SLC16A14	ENST00000457406.5	c.1067C>G	p.Thr356Arg	missense_variant	Exon 4 of 4	1		ENSP00000400352.1
SLC16A14	ENST00000412034.5	c.1067C>G	p.Thr356Arg	missense_variant	Exon 5 of 5	2		ENSP00000395775.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461842 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727212

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111970

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.64	D;.;.
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.86	D;D;D
M_CAP	Benign	0.034	D
MetaRNN	Pathogenic	0.87	D;D;D
MetaSVM	Benign	-0.30	T
MutationAssessor	Uncertain	2.5	M;.;.
PhyloP100		4.6
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-2.2	N;N;N
REVEL	Uncertain	0.36
Sift	Uncertain	0.018	D;D;D
Sift4G	Uncertain	0.0090	D;.;.
Polyphen		1.0	D;D;.
Vest4		0.88
MutPred		0.78		Gain of helix (P = 0.2059);Gain of helix (P = 0.2059);Gain of helix (P = 0.2059);
MVP		0.76
MPC		1.3
ClinPred		0.98	D
GERP RS		4.9
Varity_R		0.47
gMVP		0.98
Mutation Taster		=63/37	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: rs2077603558; hg19: chr2-230910775;