11-63290298-C-T

Variant names:

• chr11-63290298-C-T
• rs754922408
• NM_001039752.4:c.133C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001039752.4(SLC22A10):​c.133C>T​(p.Pro45Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,650 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: SLC22A10 NM_001039752.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.56
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39779037).

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.133C>T	p.Pro45Ser	missense	Exon 1 of 10	NP_001034841.3	Q63ZE4-1
	SLC22A10	NR_134874.2		n.140C>T		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.133C>T	p.Pro45Ser	missense	Exon 1 of 10	ENSP00000327569.6	Q63ZE4-1
	SLC22A10	ENST00000533483.5	TSL:1	n.-24C>T		non_coding_transcript_exon	Exon 2 of 11	ENSP00000433048.1	E9PMM0
	SLC22A10	ENST00000533483.5	TSL:1	n.-24C>T		5_prime_UTR	Exon 2 of 11	ENSP00000433048.1	E9PMM0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000800 AC: 2 AN: 249862 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461650 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 727122

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

American (AMR) AF: 0.00 AC: 0 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86236

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: 0.00000360 AC: 4 AN: 1111882

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000988 Hom.: 0

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Benign	-0.055	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Benign	0.15
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.061	N
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.40	T
MetaSVM	Uncertain	-0.090	T
MutationAssessor	Pathogenic	4.5	H
PhyloP100		1.6
PrimateAI	Benign	0.34	T
PROVEAN	Pathogenic	-7.2	D
REVEL	Benign	0.29
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.23
MutPred		0.66		Gain of helix (P = 0.2294)
MVP		0.25
MPC		0.12
ClinPred		0.99	D
GERP RS		2.9
PromoterAI		0.025	Neutral
Varity_R		0.68
gMVP		0.78
Mutation Taster		=299/1	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: rs754922408; hg19: chr11-63057770; COSMIC: COSV60421371; COSMIC: COSV60421371;