2-230045915-G-C

Variant names:

• chr2-230045915-G-C
• rs199728364
• NM_152527.5:c.1211C>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.1211C>G​(p.Thr404Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,144 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. T404A) 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: 2.50
• Publications: 7 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, 0.911

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152527.5. 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
	SLC16A14	NM_152527.5	MANE Select	c.1211C>G	p.Thr404Arg	missense	Exon 4 of 5	NP_689740.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC16A14	ENST00000295190.9	TSL:1 MANE Select	c.1211C>G	p.Thr404Arg	missense	Exon 4 of 5	ENSP00000295190.4	Q7RTX9-1
	SLC16A14	ENST00000457406.5	TSL:1	c.1211C>G	p.Thr404Arg	missense	Exon 4 of 4	ENSP00000400352.1	E7EMG7
	SLC16A14	ENST00000880807.1		c.1211C>G	p.Thr404Arg	missense	Exon 4 of 5	ENSP00000550866.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251230 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460144 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 725958

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33446

American (AMR) AF: 0.00 AC: 0 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39634

South Asian (SAS) AF: 0.00 AC: 0 AN: 86210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110540

Other (OTH) AF: 0.00 AC: 0 AN: 60340

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.054	T
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.48	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.070	D
MetaRNN	Pathogenic	0.91	D
MetaSVM	Uncertain	0.20	D
MutationAssessor	Uncertain	2.5	M
PhyloP100		2.5
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-2.5	D
REVEL	Pathogenic	0.66
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.74
MutPred		0.81		Gain of helix (P = 0.132)
MVP		0.78
MPC		1.2
ClinPred		0.96	D
GERP RS		4.8
Varity_R		0.34
gMVP		0.88
Mutation Taster		=73/27	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.24		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.24		Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs199728364; hg19: chr2-230910631;