chr11-63217396-T-C

Variant names:

• chr11-63217396-T-C
• rs11231409
• NM_199352.6:c.748A>G

Variant summary

Our verdict is Benign. The variant received -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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 29 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SLC22A25	NM_199352.6	c.748A>G	p.Ser250Gly	missense_variant	Exon 7 of 12	ENST00000306494.11	NP_955384.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A25	ENST00000306494.11	c.748A>G	p.Ser250Gly	missense_variant	Exon 7 of 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

GnomAD2 exomes AF: 0.414 AC: 103882 AN: 250892 AF XY: 0.418

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 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

African (AFR) AF: 0.319 AC: 10669 AN: 33472

American (AMR) AF: 0.463 AC: 20652 AN: 44618

Ashkenazi Jewish (ASJ) AF: 0.548 AC: 14321 AN: 26132

East Asian (EAS) AF: 0.587 AC: 23289 AN: 39658

South Asian (SAS) AF: 0.513 AC: 44227 AN: 86244

European-Finnish (FIN) AF: 0.324 AC: 17302 AN: 53396

Middle Eastern (MID) AF: 0.461 AC: 2657 AN: 5764

European-Non Finnish (NFE) AF: 0.363 AC: 403118 AN: 1111918

Other (OTH) AF: 0.396 AC: 23894 AN: 60390

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

African (AFR) AF: 0.308 AC: 12775 AN: 41464

American (AMR) AF: 0.433 AC: 6612 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.538 AC: 1866 AN: 3470

East Asian (EAS) AF: 0.564 AC: 2908 AN: 5158

South Asian (SAS) AF: 0.517 AC: 2491 AN: 4818

European-Finnish (FIN) AF: 0.333 AC: 3525 AN: 10570

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.367 AC: 24957 AN: 67960

Other (OTH) AF: 0.399 AC: 841 AN: 2110

Alfa AF: 0.378 Hom.: 37231

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
PhyloP100		0.32
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
Mutation Taster		=100/0	polymorphism (auto)

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: rs11231409; hg19: chr11-62984868; COSMIC: COSV60599130;