11-63290308-G-C

Variant names:

• chr11-63290308-G-C
• rs374307478
• NM_001039752.4:c.143G>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001039752.4(SLC22A10):​c.143G>C​(p.Arg48Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000144 in 1,461,632 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R48H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: SLC22A10 NM_001039752.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43
• Publications: 0 publications found

Genes affected

SLC22A10 (HGNC:18057): (solute carrier family 22 member 10) Predicted to enable transmembrane transporter activity. Predicted to be involved in organic anion transport. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.842

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039752.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A10	NM_001039752.4	MANE Select	c.143G>C	p.Arg48Pro	missense	Exon 1 of 10	NP_001034841.3	Q63ZE4-1
	SLC22A10	NR_134874.2		n.150G>C		non_coding_transcript_exon	Exon 2 of 11

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A10	ENST00000332793.11	TSL:1 MANE Select	c.143G>C	p.Arg48Pro	missense	Exon 1 of 10	ENSP00000327569.6	Q63ZE4-1
	SLC22A10	ENST00000532724.5	TSL:1	n.10G>C		non_coding_transcript_exon	Exon 1 of 7
	SLC22A10	ENST00000533483.5	TSL:1	n.-14G>C		non_coding_transcript_exon	Exon 2 of 11	ENSP00000433048.1	E9PMM0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000144 AC: 21 AN: 1461632 Hom.: 0 Cov.: 30 AF XY: 0.0000124 AC XY: 9 AN XY: 727108

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.00 AC: 0 AN: 86228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000189 AC: 21 AN: 1111878

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 32

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Benign	0.45	N
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.021	T
MetaRNN	Pathogenic	0.84	D
MetaSVM	Benign	-0.28	T
MutationAssessor	Pathogenic	4.1	H
PhyloP100		1.4
PrimateAI	Benign	0.35	T
PROVEAN	Pathogenic	-6.2	D
REVEL	Uncertain	0.30
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.66
MutPred		0.71		Loss of solvent accessibility (P = 0.239)
MVP		0.32
MPC		0.12
ClinPred		0.98	D
GERP RS		2.0
PromoterAI		-0.014	Neutral
Varity_R		0.67
gMVP		0.77
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs374307478; hg19: chr11-63057780;