4-71447704-AG-TC

Variant names:

• chr4-71447704-AG-TC
• NM_001098484.3:c.1024_1025delAGinsTC
• SLC4A4 p.Arg342Ser

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PS1 PP3

The NM_001098484.3(SLC4A4):​c.1024_1025delAGinsTC​(p.Arg342Ser) variant causes a missense change involving the alteration of a 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 MNV, 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Pathogenic in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC4A4 NM_001098484.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 10.0
• Publications: 0 publications found

Genes affected

SLC4A4 (HGNC:11030): (solute carrier family 4 member 4) This gene encodes a sodium bicarbonate cotransporter (NBC) involved in the regulation of bicarbonate secretion and absorption and intracellular pH. Mutations in this gene are associated with proximal renal tubular acidosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

SLC4A4 Gene-Disease associations (from GenCC):

• autosomal recessive proximal renal tubular acidosis

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia, Orphanet, Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

• PS1: Transcript NM_001098484.3 (SLC4A4) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in ClinVar.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098484.3. 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
	SLC4A4	NM_001098484.3	MANE Select	c.1024_1025delAGinsTC	p.Arg342Ser	missense	N/A	NP_001091954.1	Q9Y6R1-1
	SLC4A4	NM_003759.4	MANE Plus Clinical	c.892_893delAGinsTC	p.Arg298Ser	missense	N/A	NP_003750.1	Q9Y6R1-2
	SLC4A4	NM_001440629.1		c.1117_1118delAGinsTC	p.Arg373Ser	missense	N/A	NP_001427558.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A4	ENST00000264485.11	TSL:1 MANE Select	c.1024_1025delAGinsTC	p.Arg342Ser	missense	N/A	ENSP00000264485.5	Q9Y6R1-1
	SLC4A4	ENST00000340595.4	TSL:1 MANE Plus Clinical	c.892_893delAGinsTC	p.Arg298Ser	missense	N/A	ENSP00000344272.3	Q9Y6R1-2
	SLC4A4	ENST00000351898.10	TSL:1	c.1024_1025delAGinsTC	p.Arg342Ser	missense	N/A	ENSP00000307349.7	Q9Y6R1-4

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		10

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr4-72313421;