9-137232599-G-A

Variant names:

• chr9-137232599-G-A
• rs34372115
• NM_001177316.2:c.200G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001177316.2(SLC34A3):​c.200G>A​(p.Arg67His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.089 in 1,609,484 control chromosomes in the GnomAD database, including 7,480 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R67C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.073 (587 hom., cov: 33)
  • Exomes 𝑓: 0.091 (6893 hom.)
• Consequence: SLC34A3 NM_001177316.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.0290
• Publications: 19 publications found

Genes affected

SLC34A3 (HGNC:20305): (solute carrier family 34 member 3) This gene encodes a member of SLC34A transporter family of proteins, and is expressed primarily in the kidney. It is involved in transporting phosphate into cells via sodium cotransport in the renal brush border membrane, and contributes to the maintenance of inorganic phosphate concentration in the kidney. Mutations in this gene are associated with hereditary hypophosphatemic rickets with hypercalciuria. Alternatively spliced transcript variants varying in the 5' UTR have been found for this gene.[provided by RefSeq, Apr 2010]

SLC34A3 Gene-Disease associations (from GenCC):

• hereditary hypophosphatemic rickets with hypercalciuria

  Inheritance: AR, SD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002386719).
• BP6: Variant 9-137232599-G-A is Benign according to our data. Variant chr9-137232599-G-A is described in ClinVar as Benign. ClinVar VariationId is 504911.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001177316.2. 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
	SLC34A3	NM_001177316.2	MANE Select	c.200G>A	p.Arg67His	missense	Exon 4 of 13	NP_001170787.2	Q8N130
	SLC34A3	NM_001177317.2		c.200G>A	p.Arg67His	missense	Exon 4 of 13	NP_001170788.2	Q8N130
	SLC34A3	NM_080877.3		c.200G>A	p.Arg67His	missense	Exon 4 of 13	NP_543153.2	Q8N130

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC34A3	ENST00000673835.1	MANE Select	c.200G>A	p.Arg67His	missense	Exon 4 of 13	ENSP00000501114.1	Q8N130
	SLC34A3	ENST00000361134.2	TSL:2	c.200G>A	p.Arg67His	missense	Exon 4 of 13	ENSP00000355353.2	Q8N130
	SLC34A3	ENST00000538474.5	TSL:5	c.200G>A	p.Arg67His	missense	Exon 4 of 13	ENSP00000442397.1	Q8N130

Frequencies

GnomAD3 genomes AF: 0.0732 AC: 11091 AN: 151592 Hom.: 589 Cov.: 33

Gnomad AFR AF: 0.0151

Gnomad AMI AF: 0.0602

Gnomad AMR AF: 0.0548

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.0733

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.0944

Gnomad OTH AF: 0.0963

GnomAD2 exomes AF: 0.0987 AC: 24067 AN: 243734 AF XY: 0.105

Gnomad AFR exome AF: 0.0138

Gnomad AMR exome AF: 0.0478

Gnomad ASJ exome AF: 0.126

Gnomad EAS exome AF: 0.209

Gnomad FIN exome AF: 0.0775

Gnomad NFE exome AF: 0.0957

Gnomad OTH exome AF: 0.108

GnomAD4 exome AF: 0.0907 AC: 132217 AN: 1457780 Hom.: 6893 Cov.: 40 AF XY: 0.0937 AC XY: 67932 AN XY: 725198

African (AFR) AF: 0.0137 AC: 454 AN: 33162

American (AMR) AF: 0.0512 AC: 2283 AN: 44600

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 3247 AN: 26082

East Asian (EAS) AF: 0.183 AC: 7215 AN: 39468

South Asian (SAS) AF: 0.145 AC: 12473 AN: 86028

European-Finnish (FIN) AF: 0.0792 AC: 4116 AN: 51952

Middle Eastern (MID) AF: 0.178 AC: 1023 AN: 5758

European-Non Finnish (NFE) AF: 0.0862 AC: 95673 AN: 1110526

Other (OTH) AF: 0.0952 AC: 5733 AN: 60204

GnomAD4 genome AF: 0.0730 AC: 11076 AN: 151704 Hom.: 587 Cov.: 33 AF XY: 0.0735 AC XY: 5456 AN XY: 74194

African (AFR) AF: 0.0150 AC: 619 AN: 41176

American (AMR) AF: 0.0547 AC: 835 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 450 AN: 3472

East Asian (EAS) AF: 0.197 AC: 1020 AN: 5166

South Asian (SAS) AF: 0.137 AC: 661 AN: 4820

European-Finnish (FIN) AF: 0.0733 AC: 779 AN: 10622

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.0944 AC: 6409 AN: 67926

Other (OTH) AF: 0.0963 AC: 202 AN: 2098

Alfa AF: 0.0755 Hom.: 142

Bravo AF: 0.0688

TwinsUK AF: 0.0763 AC: 283

ALSPAC AF: 0.0913 AC: 352

ESP6500AA AF: 0.0164 AC: 72

ESP6500EA AF: 0.0895 AC: 766

ExAC AF: 0.0989 AC: 11924

EpiCase AF: 0.103

EpiControl AF: 0.105

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	8.4
DANN	Benign	0.82
DEOGEN2	Benign	0.19	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.47	T
MetaRNN	Benign	0.0024	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.029
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.018
Sift	Benign	0.58	T
Sift4G	Benign	0.45	T
Polyphen		0.0070	B
Vest4		0.060
MPC		0.046
ClinPred		0.015	T
GERP RS		-7.5
Varity_R		0.029
gMVP		0.51
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs34372115; hg19: chr9-140127051; COSMIC: COSV63186725; COSMIC: COSV63186725;