rs12210538

Variant names:

• chr6-110438805-A-G
• rs12210538
• NM_033125.4:c.1226T>C

Variant summary

Our verdict is Benign. The variant received -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.

• 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
• Publications: 57 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SLC22A16	NM_033125.4	c.1226T>C	p.Met409Thr	missense_variant	Exon 5 of 8	ENST00000368919.8	NP_149116.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A16	ENST00000368919.8	c.1226T>C	p.Met409Thr	missense_variant	Exon 5 of 8	1	NM_033125.4	ENSP00000357915.3
SLC22A16	ENST00000330550.8	c.1124T>C	p.Met375Thr	missense_variant	Exon 7 of 10	1		ENSP00000328583.4
SLC22A16	ENST00000451557.5	c.977T>C	p.Met326Thr	missense_variant	Exon 4 of 7	2		ENSP00000395642.1
SLC22A16	ENST00000434949.5	c.716T>C	p.Met239Thr	missense_variant	Exon 5 of 5	3		ENSP00000409306.1

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

GnomAD2 exomes AF: 0.169 AC: 42323 AN: 250846 AF XY: 0.175

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 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

African (AFR) AF: 0.0374 AC: 1251 AN: 33474

American (AMR) AF: 0.125 AC: 5589 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 7259 AN: 26120

East Asian (EAS) AF: 0.000554 AC: 22 AN: 39696

South Asian (SAS) AF: 0.116 AC: 10003 AN: 86200

European-Finnish (FIN) AF: 0.158 AC: 8462 AN: 53410

Middle Eastern (MID) AF: 0.262 AC: 1509 AN: 5764

European-Non Finnish (NFE) AF: 0.236 AC: 262428 AN: 1111664

Other (OTH) AF: 0.198 AC: 11978 AN: 60372

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

African (AFR) AF: 0.0412 AC: 1712 AN: 41564

American (AMR) AF: 0.159 AC: 2437 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 927 AN: 3470

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5178

South Asian (SAS) AF: 0.105 AC: 508 AN: 4824

European-Finnish (FIN) AF: 0.151 AC: 1597 AN: 10600

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.236 AC: 16061 AN: 67990

Other (OTH) AF: 0.182 AC: 386 AN: 2116

Alfa AF: 0.212 Hom.: 17425

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
DEOGEN2	Benign	0.27	.;T;.;.
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
MutationAssessor	Uncertain	2.1	.;M;.;.
PhyloP100		6.4
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
Mutation Taster		=96/4	polymorphism (auto)

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