rs11231409

chr11-63217396-T-Achr11-63217396-T-C

Variant summary

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

The NM_199352.6(SLC22A25):c.748A>T(p.Ser250Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/21 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. S250G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC22A25 NM_199352.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.316

Genes affected

SLC22A25 (HGNC:32935): (solute carrier family 22 member 25) 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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A25	NM_199352.6	c.748A>T	p.Ser250Cys	missense_variant	7/12	ENST00000306494.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A25	ENST00000306494.11	c.748A>T	p.Ser250Cys	missense_variant	7/12	1	NM_199352.6	P1
SLC22A25	ENST00000527057.5	c.745A>T	p.Ser249Cys	missense_variant, NMD_transcript_variant	4/10	1
SLC22A25	ENST00000525295.1	c.402+11855A>T		intron_variant, NMD_transcript_variant		1
SLC22A25	ENST00000528239.5	c.*397A>T		3_prime_UTR_variant, NMD_transcript_variant	6/11	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 50

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
Cadd	Benign	16
Dann	Uncertain	0.98
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.0080	T
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	1.4	L
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.19
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.97	D
Vest4		0.25
MutPred		0.54		Loss of glycosylation at S250 (P = 0.0854);
MVP		0.26
MPC		0.067
ClinPred		0.86	D
GERP RS		0.35
Varity_R		0.32
gMVP		0.091

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: rs11231409; hg19: chr11-62984868;