11-63217396-T-C

Position:

• chr11-63217396-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_199352.6(SLC22A25):​c.748A>G​(p.Ser250Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 1,613,600 control chromosomes in the GnomAD database, including 121,061 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.37 (10760 hom., cov: 32)
  • Exomes 𝑓: 0.38 (110301 hom.)
• 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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.236864E-4).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A25	NM_199352.6	c.748A>G	p.Ser250Gly	missense_variant	7/12	ENST00000306494.11	NP_955384.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A25	ENST00000306494.11	c.748A>G	p.Ser250Gly	missense_variant	7/12	1	NM_199352.6	ENSP00000307443.6

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56466 AN: 151890 Hom.: 10751 Cov.: 32

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.538

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.393

GnomAD3 exomes AF: 0.414 AC: 103882 AN: 250892 Hom.: 22349 AF XY: 0.418 AC XY: 56672 AN XY: 135590

Gnomad AFR exome AF: 0.307

Gnomad AMR exome AF: 0.462

Gnomad ASJ exome AF: 0.536

Gnomad EAS exome AF: 0.573

Gnomad SAS exome AF: 0.516

Gnomad FIN exome AF: 0.327

Gnomad NFE exome AF: 0.368

Gnomad OTH exome AF: 0.410

GnomAD4 exome AF: 0.383 AC: 560129 AN: 1461592 Hom.: 110301 Cov.: 50 AF XY: 0.387 AC XY: 281703 AN XY: 727100

Gnomad4 AFR exome AF: 0.319

Gnomad4 AMR exome AF: 0.463

Gnomad4 ASJ exome AF: 0.548

Gnomad4 EAS exome AF: 0.587

Gnomad4 SAS exome AF: 0.513

Gnomad4 FIN exome AF: 0.324

Gnomad4 NFE exome AF: 0.363

Gnomad4 OTH exome AF: 0.396

GnomAD4 genome AF: 0.372 AC: 56516 AN: 152008 Hom.: 10760 Cov.: 32 AF XY: 0.377 AC XY: 28017 AN XY: 74312

Gnomad4 AFR AF: 0.308

Gnomad4 AMR AF: 0.433

Gnomad4 ASJ AF: 0.538

Gnomad4 EAS AF: 0.564

Gnomad4 SAS AF: 0.517

Gnomad4 FIN AF: 0.333

Gnomad4 NFE AF: 0.367

Gnomad4 OTH AF: 0.399

Alfa AF: 0.380 Hom.: 27835

Bravo AF: 0.375

TwinsUK AF: 0.368 AC: 1363

ALSPAC AF: 0.371 AC: 1428

ESP6500AA AF: 0.318 AC: 1399

ESP6500EA AF: 0.379 AC: 3259

ExAC AF: 0.409 AC: 49685

Asia WGS AF: 0.503 AC: 1752 AN: 3478

EpiCase AF: 0.377

EpiControl AF: 0.375

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.045
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	0.43
DANN	Benign	0.53
DEOGEN2	Benign	0.039	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.00054	N
LIST_S2	Benign	0.044	T
MetaRNN	Benign	0.00052	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-2.2	N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	3.8	N
REVEL	Benign	0.15
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.027
MPC		0.014
ClinPred		0.0066	T
GERP RS		0.35
Varity_R		0.039
gMVP		0.076

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; COSMIC: COSV60599130;