rs714368

Positions:

• chr6-110456925-T-C
• chr6-110456925-T-G

Variant summary

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

The NM_033125.4(SLC22A16):​c.146A>G​(p.His49Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 1,612,452 control chromosomes in the GnomAD database, including 48,459 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict 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 0.27 (6035 hom., cov: 31)
  • Exomes 𝑓: 0.24 (42424 hom.)
• Consequence: SLC22A16 NM_033125.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.846

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=0.0010417104).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A16	NM_033125.4	c.146A>G	p.His49Arg	missense_variant	2/8	ENST00000368919.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A16	ENST00000368919.8	c.146A>G	p.His49Arg	missense_variant	2/8	1	NM_033125.4	P2

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41216 AN: 151832 Hom.: 6029 Cov.: 31

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.270

GnomAD3 exomes AF: 0.251 AC: 62879 AN: 250274 Hom.: 8483 AF XY: 0.249 AC XY: 33683 AN XY: 135226

Gnomad AFR exome AF: 0.370

Gnomad AMR exome AF: 0.225

Gnomad ASJ exome AF: 0.304

Gnomad EAS exome AF: 0.416

Gnomad SAS exome AF: 0.275

Gnomad FIN exome AF: 0.180

Gnomad NFE exome AF: 0.218

Gnomad OTH exome AF: 0.246

GnomAD4 exome AF: 0.236 AC: 344502 AN: 1460502 Hom.: 42424 Cov.: 34 AF XY: 0.237 AC XY: 171874 AN XY: 726406

Gnomad4 AFR exome AF: 0.369

Gnomad4 AMR exome AF: 0.221

Gnomad4 ASJ exome AF: 0.305

Gnomad4 EAS exome AF: 0.428

Gnomad4 SAS exome AF: 0.273

Gnomad4 FIN exome AF: 0.190

Gnomad4 NFE exome AF: 0.222

Gnomad4 OTH exome AF: 0.257

GnomAD4 genome AF: 0.271 AC: 41254 AN: 151950 Hom.: 6035 Cov.: 31 AF XY: 0.269 AC XY: 19947 AN XY: 74270

Gnomad4 AFR AF: 0.372

Gnomad4 AMR AF: 0.231

Gnomad4 ASJ AF: 0.314

Gnomad4 EAS AF: 0.430

Gnomad4 SAS AF: 0.262

Gnomad4 FIN AF: 0.188

Gnomad4 NFE AF: 0.219

Gnomad4 OTH AF: 0.268

Alfa AF: 0.231 Hom.: 9714

Bravo AF: 0.280

TwinsUK AF: 0.234 AC: 868

ALSPAC AF: 0.223 AC: 859

ESP6500AA AF: 0.363 AC: 1600

ESP6500EA AF: 0.223 AC: 1917

ExAC AF: 0.254 AC: 30824

Asia WGS AF: 0.342 AC: 1185 AN: 3478

EpiCase AF: 0.233

EpiControl AF: 0.230

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	0.048
DANN	Benign	0.19
DEOGEN2	Benign	0.0092	T;.;.;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.099	N
LIST_S2	Benign	0.060	T;T;T;T
MetaRNN	Benign	0.0010	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.55	N;.;.;.
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.20	T
PROVEAN	Benign	0.15	N;N;N;N
REVEL	Benign	0.20
Sift	Benign	0.16	T;T;T;T
Sift4G	Benign	0.62	T;T;.;T
Polyphen		0.0	B;B;.;.
Vest4		0.022
MPC		0.016
ClinPred		0.0076	T
GERP RS		-3.1
Varity_R		0.029
gMVP		0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs714368; hg19: chr6-110778128; COSMIC: COSV57930020; COSMIC: COSV57930020;