Genetic Variant SLC34A1:p.Val91_Ala97dup (chr5-177386231-G-GGTCCCCAAGCTGCGCCAGGCT) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM4

The NM_003052.5(SLC34A1):c.272_292dupTCCCCAAGCTGCGCCAGGCTG(p.Val91_Ala97dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G98G) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

SLC34A1
NM_003052.5 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.324

Publications

0 publications found

Variant links:

Genes affected

SLC34A1 (HGNC:11019): (solute carrier family 34 member 1) Enables sodium:phosphate symporter activity. Involved in several processes, including phosphate ion homeostasis; phosphate ion transport; and response to lead ion. Located in several cellular components, including apical plasma membrane; mitotic spindle; and nuclear speck. Implicated in several diseases, including Fanconi syndrome (multiple); chronic kidney disease; hereditary hypophosphatemic rickets with hypercalciuria; hypophosphatemic nephrolithiasis/osteoporosis 1; and nephrolithiasis. [provided by Alliance of Genome Resources, Apr 2022]

SLC34A1 Gene-Disease associations (from GenCC):

hypercalcemia, infantile, 2
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen
dominant hypophosphatemia with nephrolithiasis or osteoporosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
primary Fanconi syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
autosomal recessive infantile hypercalcemia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
hypophosphatemic nephrolithiasis/osteoporosis 1
Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
Fanconi renotubular syndrome 2
Inheritance: AR Classification: LIMITED, NO_KNOWN Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)

SLC34A1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_003052.5.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003052.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC34A1	NM_003052.5	MANE Select	c.272_292dupTCCCCAAGCTGCGCCAGGCTG	p.Val91_Ala97dup	disruptive_inframe_insertion	Exon 4 of 13	NP_003043.3
	SLC34A1	NM_001167579.2		c.272_292dupTCCCCAAGCTGCGCCAGGCTG	p.Val91_Ala97dup	disruptive_inframe_insertion	Exon 4 of 9	NP_001161051.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SLC34A1	ENST00000324417.6	TSL:1 MANE Select	c.272_292dupTCCCCAAGCTGCGCCAGGCTG	p.Val91_Ala97dup	disruptive_inframe_insertion	Exon 4 of 13	ENSP00000321424.4
SLC34A1	ENST00000512593.5	TSL:2	c.272_292dupTCCCCAAGCTGCGCCAGGCTG	p.Val91_Ala97dup	disruptive_inframe_insertion	Exon 4 of 9	ENSP00000423022.1
SLC34A1	ENST00000504577.5	TSL:4	c.272_292dupTCCCCAAGCTGCGCCAGGCTG	p.Val91_Ala97dup	disruptive_inframe_insertion	Exon 4 of 4	ENSP00000423733.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.32

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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5-177386231-GGTCCCCAAGCTGCGCCAGGCT-GGTCCCCAAGCTGCGCCAGGCTGTCCCCAAGCTGCGCCAGGCT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over