chr2-74255906-G-GA

Variant names:

• chr2-74255906-G-GA
• rs35866044
• NM_133478.3:c.893dupT

Variant summary

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

The NM_133478.3(SLC4A5):​c.893dupT​(p.Lys300GlnfsTer60) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC4A5 NM_133478.3 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.28
• Publications: 1 publications found

Genes affected

SLC4A5 (HGNC:18168): (solute carrier family 4 member 5) This gene encodes a member of the sodium bicarbonate cotransporter (NBC) family, part of the bicarbonate transporter superfamily. Sodium bicarbonate cotransporters are involved in intracellular pH regulation and electroneural or electrogenic sodium bicarbonate transport. This protein is thought to be an integral membrane protein. Multiple transcript variants encoding different isoforms have been found for this gene, but the biological validity of some variants has not been determined. [provided by RefSeq, Jul 2008]

ENSG00000264324 (HGNC:):

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC4A5	NM_133478.3	c.893dupT	p.Lys300GlnfsTer60	frameshift_variant	Exon 13 of 31	ENST00000394019.7	NP_597812.1
SLC4A5	NM_021196.3	c.893dupT	p.Lys300GlnfsTer60	frameshift_variant	Exon 8 of 26		NP_067019.3
SLC4A5	NM_001386136.1	c.545dupT	p.Lys184GlnfsTer60	frameshift_variant	Exon 7 of 25		NP_001373065.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC4A5	ENST00000394019.7	c.893dupT	p.Lys300GlnfsTer60	frameshift_variant	Exon 13 of 31	5	NM_133478.3	ENSP00000377587.2
ENSG00000264324	ENST00000451608.2	n.*1481dupT		non_coding_transcript_exon_variant	Exon 18 of 39	5		ENSP00000416453.2
ENSG00000264324	ENST00000451608.2	n.*1481dupT		3_prime_UTR_variant	Exon 18 of 39	5		ENSP00000416453.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.3
Mutation Taster		=6/194	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs35866044; hg19: chr2-74483033;