rs6448389

Variant names:

• chr4-25676577-A-C
• rs6448389
• NM_006424.3:c.1901A>C

Your query was ambiguous. Multiple possible variants found:

• chr4-25676577-A-C
• chr4-25676577-A-G
• chr4-25676577-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006424.3(SLC34A2):​c.1901A>C​(p.Asp634Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. D634G) has been classified as Benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: SLC34A2 NM_006424.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.01
• Publications: 27 publications found

Genes affected

SLC34A2 (HGNC:11020): (solute carrier family 34 member 2) The protein encoded by this gene is a pH-sensitive sodium-dependent phosphate transporter. Phosphate uptake is increased at lower pH. Defects in this gene are a cause of pulmonary alveolar microlithiasis. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, May 2010]

SLC34A2 Gene-Disease associations (from GenCC):

• pulmonary alveolar microlithiasis

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.103236645).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC34A2	NM_006424.3	c.1901A>C	p.Asp634Ala	missense_variant	Exon 13 of 13	ENST00000382051.8	NP_006415.3
SLC34A2	NM_001177998.2	c.1898A>C	p.Asp633Ala	missense_variant	Exon 13 of 13		NP_001171469.2
SLC34A2	NM_001177999.2	c.1898A>C	p.Asp633Ala	missense_variant	Exon 13 of 13		NP_001171470.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC34A2	ENST00000382051.8	c.1901A>C	p.Asp634Ala	missense_variant	Exon 13 of 13	1	NM_006424.3	ENSP00000371483.3
SLC34A2	ENST00000503434.5	c.1898A>C	p.Asp633Ala	missense_variant	Exon 13 of 13	1		ENSP00000423021.1
SLC34A2	ENST00000504570.5	c.1898A>C	p.Asp633Ala	missense_variant	Exon 13 of 13	1		ENSP00000425501.1
SLC34A2	ENST00000645788.1	c.1898A>C	p.Asp633Ala	missense_variant	Exon 13 of 13			ENSP00000494094.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 49

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	16
DANN	Benign	0.79
DEOGEN2	Benign	0.021	.;.;T;.
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.26	.;.;T;T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.10	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	.;.;N;.
PhyloP100		2.0
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.24	.;N;N;N
REVEL	Benign	0.055
Sift	Uncertain	0.010	.;D;D;D
Sift4G	Benign	0.35	.;T;T;T
Polyphen		0.0	B;B;B;B
Vest4		0.12, 0.11, 0.13
MutPred		0.21		.;.;Loss of glycosylation at K637 (P = 0.0297);.;
MVP		0.35
MPC		0.30
ClinPred		0.52	D
GERP RS		5.0
Varity_R		0.067
gMVP		0.42
Mutation Taster		=100/0	polymorphism

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: rs6448389; hg19: chr4-25678199;