chr6-160348705-G-C

Variant names:

• chr6-160348705-G-C
• rs1469600200
• NM_021977.4:c.286G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_021977.4(SLC22A3):​c.286G>C​(p.Glu96Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC22A3 NM_021977.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.22

Genes affected

SLC22A3 (HGNC:10967): (solute carrier family 22 member 3) Polyspecific organic cation transporters in the liver, kidney, intestine, and other organs are critical for elimination of many endogenous small organic cations as well as a wide array of drugs and environmental toxins. This gene is one of three similar cation transporter genes located in a cluster on chromosome 6. The encoded protein contains twelve putative transmembrane domains and is a plasma integral membrane protein. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26888466).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A3	NM_021977.4	c.286G>C	p.Glu96Gln	missense_variant	Exon 1 of 11	ENST00000275300.3	NP_068812.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A3	ENST00000275300.3	c.286G>C	p.Glu96Gln	missense_variant	Exon 1 of 11	1	NM_021977.4	ENSP00000275300.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1369734 Hom.: 0 Cov.: 68 AF XY: 0.00 AC XY: 0 AN XY: 675572

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 12, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.286G>C (p.E96Q) alteration is located in exon 1 (coding exon 1) of the SLC22A3 gene. This alteration results from a G to C substitution at nucleotide position 286, causing the glutamic acid (E) at amino acid position 96 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Benign	0.012
Eigen_PC	Benign	0.078
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.4	L
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.15
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.013	D
Polyphen		0.73	P
Vest4		0.18
MutPred		0.41		Gain of MoRF binding (P = 0.0255);
MVP		0.81
MPC		0.42
ClinPred		0.84	D
GERP RS		4.0
Varity_R		0.23
gMVP		0.63

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: rs1469600200; hg19: chr6-160769737;