6-110438737-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_033125.4(SLC22A16):c.1294G>A(p.Val432Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00129 in 1,613,438 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0055 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00084 (12 hom.)
• Consequence: SLC22A16 NM_033125.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.162

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0043098927).
• BP6: Variant 6-110438737-C-T is Benign according to our data. Variant chr6-110438737-C-T is described in ClinVar as [Benign]. Clinvar id is 712559.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00554 (843/152268) while in subpopulation AFR AF= 0.0173 (720/41550). AF 95% confidence interval is 0.0163. There are 2 homozygotes in gnomad4. There are 395 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A16	NM_033125.4	c.1294G>A	p.Val432Ile	missense_variant	5/8	ENST00000368919.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A16	ENST00000368919.8	c.1294G>A	p.Val432Ile	missense_variant	5/8	1	NM_033125.4	P2
SLC22A16	ENST00000330550.8	c.1192G>A	p.Val398Ile	missense_variant	7/10	1		A2
SLC22A16	ENST00000451557.5	c.1045G>A	p.Val349Ile	missense_variant	4/7	2
SLC22A16	ENST00000434949.5	c.784G>A	p.Val262Ile	missense_variant	5/5	3

Frequencies

GnomAD3 genomes AF: 0.00551 AC: 839 AN: 152152 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.0173

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00550

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00178 AC: 446 AN: 250056 Hom.: 1 AF XY: 0.00142 AC XY: 192 AN XY: 135062

Gnomad AFR exome AF: 0.0174

Gnomad AMR exome AF: 0.00215

Gnomad ASJ exome AF: 0.000299

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000524

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000470

Gnomad OTH exome AF: 0.00280

GnomAD4 exome AF: 0.000842 AC: 1231 AN: 1461170 Hom.: 12 Cov.: 30 AF XY: 0.000790 AC XY: 574 AN XY: 726868

Gnomad4 AFR exome AF: 0.0175

Gnomad4 AMR exome AF: 0.00260

Gnomad4 ASJ exome AF: 0.000307

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.000476

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000322

Gnomad4 OTH exome AF: 0.00177

GnomAD4 genome AF: 0.00554 AC: 843 AN: 152268 Hom.: 2 Cov.: 32 AF XY: 0.00531 AC XY: 395 AN XY: 74454

Gnomad4 AFR AF: 0.0173

Gnomad4 AMR AF: 0.00549

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000368

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00126 Hom.: 1

Bravo AF: 0.00592

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0170 AC: 75

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00206 AC: 250

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.000710

EpiControl AF: 0.000475

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 21, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.67
Cadd	Benign	0.015
Dann	Benign	0.78
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0032	N
LIST_S2	Benign	0.36	T;T;T;T
MetaRNN	Benign	0.0043	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.20	T
PROVEAN	Benign	0.15	N;N;N;N
REVEL	Benign	0.066
Sift	Benign	1.0	T;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.0010, 0.0	.;B;B;.
Vest4		0.076, 0.077
MVP		0.095
MPC		0.015
ClinPred		0.00081	T
GERP RS		-1.1
Varity_R		0.035
gMVP		0.16

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: rs75035916; hg19: chr6-110759940;