NM_007163.4:c.2638G>A

Variant names:

• chr18-45682394-G-A
• rs3745009
• NM_007163.4:c.2638G>A

Variant summary

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

The NM_007163.4(SLC14A2):​c.2638G>A​(p.Ala880Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 1,613,370 control chromosomes in the GnomAD database, including 159,508 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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 0.43 (14034 hom., cov: 31)
  • Exomes 𝑓: 0.44 (145474 hom.)
• Consequence: SLC14A2 NM_007163.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.09
• Publications: 32 publications found

Genes affected

SLC14A2 (HGNC:10919): (solute carrier family 14 member 2) The protein encoded by this gene belongs to the urea transporter family. In mammalian cells, urea is the chief end product of nitrogen catabolism, and plays an important role in the urinary concentration mechanism. This protein is expressed in the inner medulla of the kidney, and mediates rapid transepithelial urea transport across the inner medullary collecting duct. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2011]

ENSG00000288545 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0030146837).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007163.4. 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
	SLC14A2	NM_007163.4	MANE Select	c.2638G>A	p.Ala880Thr	missense	Exon 20 of 20	NP_009094.3
	SLC14A2	NM_001242692.2		c.2638G>A	p.Ala880Thr	missense	Exon 21 of 21	NP_001229621.1	Q15849-1
	SLC14A2	NM_001371319.1		c.2638G>A	p.Ala880Thr	missense	Exon 24 of 24	NP_001358248.1	Q15849-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC14A2	ENST00000255226.11	TSL:1 MANE Select	c.2638G>A	p.Ala880Thr	missense	Exon 20 of 20	ENSP00000255226.5	Q15849-1
	SLC14A2	ENST00000586448.5	TSL:2	c.2638G>A	p.Ala880Thr	missense	Exon 21 of 21	ENSP00000465953.1	Q15849-1
	ENSG00000288545	ENST00000589510.5	TSL:5	n.206+10001C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64683 AN: 151712 Hom.: 14026 Cov.: 31

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.461

Gnomad AMR AF: 0.404

Gnomad ASJ AF: 0.489

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.451

Gnomad OTH AF: 0.435

GnomAD2 exomes AF: 0.436 AC: 109677 AN: 251386 AF XY: 0.442

Gnomad AFR exome AF: 0.384

Gnomad AMR exome AF: 0.372

Gnomad ASJ exome AF: 0.487

Gnomad EAS exome AF: 0.407

Gnomad FIN exome AF: 0.445

Gnomad NFE exome AF: 0.445

Gnomad OTH exome AF: 0.436

GnomAD4 exome AF: 0.445 AC: 650075 AN: 1461540 Hom.: 145474 Cov.: 46 AF XY: 0.447 AC XY: 325110 AN XY: 727118

African (AFR) AF: 0.381 AC: 12767 AN: 33476

American (AMR) AF: 0.377 AC: 16839 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 12758 AN: 26134

East Asian (EAS) AF: 0.401 AC: 15937 AN: 39698

South Asian (SAS) AF: 0.493 AC: 42516 AN: 86252

European-Finnish (FIN) AF: 0.442 AC: 23584 AN: 53416

Middle Eastern (MID) AF: 0.487 AC: 2810 AN: 5766

European-Non Finnish (NFE) AF: 0.446 AC: 495831 AN: 1111692

Other (OTH) AF: 0.448 AC: 27033 AN: 60384

GnomAD4 genome AF: 0.426 AC: 64727 AN: 151830 Hom.: 14034 Cov.: 31 AF XY: 0.428 AC XY: 31749 AN XY: 74166

African (AFR) AF: 0.380 AC: 15725 AN: 41384

American (AMR) AF: 0.403 AC: 6156 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.489 AC: 1697 AN: 3470

East Asian (EAS) AF: 0.398 AC: 2048 AN: 5146

South Asian (SAS) AF: 0.494 AC: 2371 AN: 4798

European-Finnish (FIN) AF: 0.442 AC: 4644 AN: 10510

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.451 AC: 30628 AN: 67952

Other (OTH) AF: 0.432 AC: 910 AN: 2106

Alfa AF: 0.441 Hom.: 22990

Bravo AF: 0.418

TwinsUK AF: 0.451 AC: 1671

ALSPAC AF: 0.443 AC: 1707

ESP6500AA AF: 0.390 AC: 1720

ESP6500EA AF: 0.450 AC: 3870

ExAC AF: 0.436 AC: 52950

Asia WGS AF: 0.432 AC: 1499 AN: 3478

EpiCase AF: 0.456

EpiControl AF: 0.444

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.097
Eigen_PC	Benign	0.071
FATHMM_MKL	Uncertain	0.87	D
MetaRNN	Benign	0.0030	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		2.1
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.80	N
REVEL	Benign	0.062
Sift	Benign	0.41	T
Sift4G	Benign	0.34	T
Polyphen		0.017	B
Vest4		0.059
MPC		0.081
ClinPred		0.016	T
GERP RS		5.1
Varity_R		0.092
gMVP		0.83
Mutation Taster		=92/8	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: rs3745009; hg19: chr18-43262359; COSMIC: COSV54906325; COSMIC: COSV54906325;