rs12210538

chr6-110438805-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033125.4(SLC22A16):c.1226T>C(p.Met409Thr) variant causes a missense change. The variant allele was found at a frequency of 0.206 in 1,613,622 control chromosomes in the GnomAD database, including 37,919 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.16 (2501 hom., cov: 32)
  • Exomes 𝑓: 0.21 (35418 hom.)
• Consequence: SLC22A16 NM_033125.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.41

Genes affected

SLC22A16 (HGNC:20302): (solute carrier family 22 member 16) This gene encodes a member of the organic zwitterion transporter protein family which transports carnitine. The encoded protein has also been shown to transport anticancer drugs like bleomycin (PMID: 20037140) successful treatment has been correlated with the level of activity of this transporter in tumor cells. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0019080639).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A16	NM_033125.4	c.1226T>C	p.Met409Thr	missense_variant	5/8	ENST00000368919.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A16	ENST00000368919.8	c.1226T>C	p.Met409Thr	missense_variant	5/8	1	NM_033125.4	P2
SLC22A16	ENST00000330550.8	c.1124T>C	p.Met375Thr	missense_variant	7/10	1		A2
SLC22A16	ENST00000451557.5	c.977T>C	p.Met326Thr	missense_variant	4/7	2
SLC22A16	ENST00000434949.5	c.716T>C	p.Met239Thr	missense_variant	5/5	3

Frequencies

GnomAD3 genomes AF: 0.158 AC: 23988 AN: 152126 Hom.: 2500 Cov.: 32

Gnomad AFR AF: 0.0413

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.184

GnomAD3 exomes AF: 0.169 AC: 42323 AN: 250846 Hom.: 4566 AF XY: 0.175 AC XY: 23727 AN XY: 135568

Gnomad AFR exome AF: 0.0381

Gnomad AMR exome AF: 0.117

Gnomad ASJ exome AF: 0.274

Gnomad EAS exome AF: 0.000381

Gnomad SAS exome AF: 0.113

Gnomad FIN exome AF: 0.159

Gnomad NFE exome AF: 0.236

Gnomad OTH exome AF: 0.203

GnomAD4 exome AF: 0.211 AC: 308501 AN: 1461378 Hom.: 35418 Cov.: 32 AF XY: 0.210 AC XY: 152678 AN XY: 727002

Gnomad4 AFR exome AF: 0.0374

Gnomad4 AMR exome AF: 0.125

Gnomad4 ASJ exome AF: 0.278

Gnomad4 EAS exome AF: 0.000554

Gnomad4 SAS exome AF: 0.116

Gnomad4 FIN exome AF: 0.158

Gnomad4 NFE exome AF: 0.236

Gnomad4 OTH exome AF: 0.198

GnomAD4 genome AF: 0.158 AC: 23989 AN: 152244 Hom.: 2501 Cov.: 32 AF XY: 0.153 AC XY: 11382 AN XY: 74434

Gnomad4 AFR AF: 0.0412

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.267

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.236

Gnomad4 OTH AF: 0.182

Alfa AF: 0.223 Hom.: 9175

Bravo AF: 0.157

TwinsUK AF: 0.226 AC: 839

ALSPAC AF: 0.232 AC: 896

ESP6500AA AF: 0.0511 AC: 225

ESP6500EA AF: 0.243 AC: 2091

ExAC AF: 0.168 AC: 20377

Asia WGS AF: 0.0510 AC: 179 AN: 3478

EpiCase AF: 0.253

EpiControl AF: 0.253

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.17
Cadd	Benign	20
Dann	Benign	0.93
Eigen	Uncertain	0.28
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.74	T;T;T;T
MetaRNN	Benign	0.0019	T;T;T;T
MetaSVM	Uncertain	-0.14	T
MutationTaster	Benign	0.057	P;P;P
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-4.2	D;D;D;D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0040	D;D;D;D
Sift4G	Uncertain	0.0060	D;D;D;D
Polyphen		0.96, 0.95	.;D;P;.
Vest4		0.46, 0.29
MPC		0.095
ClinPred		0.049	T
GERP RS		5.0
Varity_R		0.64
gMVP		0.85

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

LitVar

Other links and lift over

dbSNP: rs12210538; hg19: chr6-110760008; COSMIC: COSV57926896; COSMIC: COSV57926896;