7-123169180-T-C

Variant names:

• chr7-123169180-T-C
• rs2140516
• NM_022444.4:c.521A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022444.4(SLC13A1):​c.521A>G​(p.Asn174Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 1,613,600 control chromosomes in the GnomAD database, including 80,570 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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 0.30 (6976 hom., cov: 32)
  • Exomes 𝑓: 0.31 (73594 hom.)
• Consequence: SLC13A1 NM_022444.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.369
• Publications: 40 publications found

Genes affected

SLC13A1 (HGNC:10916): (solute carrier family 13 member 1) The protein encoded by this gene is an apical membrane Na(+)-sulfate cotransporter involved in sulfate homeostasis in the kidney. Defects in this gene lead to many pathophysiologic problems. [provided by RefSeq, May 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006528437).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC13A1	NM_022444.4	c.521A>G	p.Asn174Ser	missense_variant	Exon 4 of 15	ENST00000194130.7	NP_071889.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC13A1	ENST00000194130.7	c.521A>G	p.Asn174Ser	missense_variant	Exon 4 of 15	1	NM_022444.4	ENSP00000194130.2

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45567 AN: 151900 Hom.: 6969 Cov.: 32

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.296

GnomAD2 exomes AF: 0.305 AC: 76463 AN: 250990 AF XY: 0.304

Gnomad AFR exome AF: 0.272

Gnomad AMR exome AF: 0.283

Gnomad ASJ exome AF: 0.285

Gnomad EAS exome AF: 0.353

Gnomad FIN exome AF: 0.341

Gnomad NFE exome AF: 0.318

Gnomad OTH exome AF: 0.310

GnomAD4 exome AF: 0.315 AC: 459795 AN: 1461582 Hom.: 73594 Cov.: 37 AF XY: 0.312 AC XY: 227209 AN XY: 727072

African (AFR) AF: 0.273 AC: 9152 AN: 33476

American (AMR) AF: 0.277 AC: 12393 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 7457 AN: 26128

East Asian (EAS) AF: 0.387 AC: 15370 AN: 39690

South Asian (SAS) AF: 0.249 AC: 21503 AN: 86250

European-Finnish (FIN) AF: 0.346 AC: 18452 AN: 53402

Middle Eastern (MID) AF: 0.222 AC: 1277 AN: 5764

European-Non Finnish (NFE) AF: 0.320 AC: 356023 AN: 1111790

Other (OTH) AF: 0.301 AC: 18168 AN: 60376

GnomAD4 genome AF: 0.300 AC: 45603 AN: 152018 Hom.: 6976 Cov.: 32 AF XY: 0.298 AC XY: 22148 AN XY: 74298

African (AFR) AF: 0.279 AC: 11560 AN: 41458

American (AMR) AF: 0.258 AC: 3936 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 972 AN: 3470

East Asian (EAS) AF: 0.349 AC: 1797 AN: 5148

South Asian (SAS) AF: 0.240 AC: 1160 AN: 4826

European-Finnish (FIN) AF: 0.327 AC: 3452 AN: 10558

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.319 AC: 21671 AN: 67962

Other (OTH) AF: 0.291 AC: 615 AN: 2110

Alfa AF: 0.312 Hom.: 36751

Bravo AF: 0.294

TwinsUK AF: 0.307 AC: 1138

ALSPAC AF: 0.316 AC: 1217

ESP6500AA AF: 0.277 AC: 1220

ESP6500EA AF: 0.315 AC: 2710

ExAC AF: 0.307 AC: 37296

Asia WGS AF: 0.255 AC: 886 AN: 3478

EpiCase AF: 0.321

EpiControl AF: 0.319

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.053
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.54
DANN	Benign	0.39
DEOGEN2	Benign	0.050	T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.55	T;T
MetaRNN	Benign	0.0065	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;.
PhyloP100		-0.37
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.51	N;N
REVEL	Benign	0.023
Sift	Benign	0.41	T;T
Sift4G	Benign	0.64	T;T
Polyphen		0.0	B;.
Vest4		0.049
MPC		0.065
ClinPred		0.0010	T
GERP RS		-4.7
Varity_R		0.026
gMVP		0.14
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2140516; hg19: chr7-122809234; COSMIC: COSV52009367;