6-110456925-T-G

Position:

• chr6-110456925-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033125.4(SLC22A16):​c.146A>C​(p.His49Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,772 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H49R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12120482).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A16	NM_033125.4	c.146A>C	p.His49Pro	missense_variant	2/8	ENST00000368919.8	NP_149116.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A16	ENST00000368919.8	c.146A>C	p.His49Pro	missense_variant	2/8	1	NM_033125.4	ENSP00000357915	P2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460772 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 726550

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.049	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	0.088
DANN	Benign	0.37
DEOGEN2	Benign	0.019	T;.;.;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.20	T;T;T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.12	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.73	N;.;.;.
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-1.3	N;N;N;N
REVEL	Benign	0.28
Sift	Uncertain	0.014	D;T;D;T
Sift4G	Benign	0.092	T;T;.;T
Polyphen		0.0010	B;B;.;.
Vest4		0.11
MutPred		0.44		Gain of catalytic residue at P48 (P = 0.0183);.;.;.;
MVP		0.055
MPC		0.016
ClinPred		0.075	T
GERP RS		-3.1
Varity_R		0.12
gMVP		0.70

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: rs714368; hg19: chr6-110778128;