6-110456925-T-C

Variant names:

• chr6-110456925-T-C
• rs714368
• NM_033125.4:c.146A>G

Variant summary

Our verdict is Benign. The variant received -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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 62 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=0.0010417104).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033125.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A16	NM_033125.4	MANE Select	c.146A>G	p.His49Arg	missense	Exon 2 of 8	NP_149116.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A16	ENST00000368919.8	TSL:1 MANE Select	c.146A>G	p.His49Arg	missense	Exon 2 of 8	ENSP00000357915.3
	SLC22A16	ENST00000330550.8	TSL:1	c.140A>G	p.His47Arg	missense	Exon 3 of 10	ENSP00000328583.4
	SLC22A16	ENST00000461487.1	TSL:1	n.213A>G		non_coding_transcript_exon	Exon 2 of 2

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

GnomAD2 exomes AF: 0.251 AC: 62879 AN: 250274 AF XY: 0.249

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 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

African (AFR) AF: 0.369 AC: 12330 AN: 33418

American (AMR) AF: 0.221 AC: 9849 AN: 44624

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 7952 AN: 26040

East Asian (EAS) AF: 0.428 AC: 16992 AN: 39676

South Asian (SAS) AF: 0.273 AC: 23441 AN: 86006

European-Finnish (FIN) AF: 0.190 AC: 10126 AN: 53378

Middle Eastern (MID) AF: 0.256 AC: 1475 AN: 5756

European-Non Finnish (NFE) AF: 0.222 AC: 246853 AN: 1111268

Other (OTH) AF: 0.257 AC: 15484 AN: 60336

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

African (AFR) AF: 0.372 AC: 15408 AN: 41404

American (AMR) AF: 0.231 AC: 3525 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.314 AC: 1089 AN: 3468

East Asian (EAS) AF: 0.430 AC: 2221 AN: 5160

South Asian (SAS) AF: 0.262 AC: 1262 AN: 4812

European-Finnish (FIN) AF: 0.188 AC: 1981 AN: 10562

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.219 AC: 14888 AN: 67966

Other (OTH) AF: 0.268 AC: 564 AN: 2104

Alfa AF: 0.239 Hom.: 20315

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 v4.9

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
MetaRNN	Benign	0.0010	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.55	N
PhyloP100		0.85
PrimateAI	Benign	0.20	T
PROVEAN	Benign	0.15	N
REVEL	Benign	0.20
Sift	Benign	0.16	T
Sift4G	Benign	0.62	T
Polyphen		0.0	B
Vest4		0.022
MPC		0.016
ClinPred		0.0076	T
GERP RS		-3.1
PromoterAI		0.031	Neutral
Varity_R		0.029
gMVP		0.32
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs714368; hg19: chr6-110778128; COSMIC: COSV57930020; COSMIC: COSV57930020;