22-32220963-TGC-ACT

Variant names:

• chr22-32220963-TGC-ACT
• NM_014227.3:c.1723_1725delGCAinsAGT
• SLC5A4 p.Ala575Ser

Variant summary

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

The NM_014227.3(SLC5A4):​c.1723_1725delGCAinsAGT​(p.Ala575Ser) variant causes a missense 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 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 Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC5A4 NM_014227.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.46
• Publications: 0 publications found

Genes affected

SLC5A4 (HGNC:11039): (solute carrier family 5 member 4) Predicted to enable glucose:sodium symporter activity and proton transmembrane transporter activity. Predicted to be involved in sodium ion transport. Predicted to act upstream of or within proton transmembrane transport. Predicted to be active in plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC5A4-AS1 (HGNC:53163): (SLC5A4 antisense RNA 1)

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014227.3. 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
	SLC5A4	NM_014227.3	MANE Select	c.1723_1725delGCAinsAGT	p.Ala575Ser	missense	N/A	NP_055042.1	Q9NY91
	SLC5A4-AS1	NR_149072.1		n.274+13687_274+13689delTGCinsACT		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC5A4	ENST00000266086.6	TSL:1 MANE Select	c.1723_1725delGCAinsAGT	p.Ala575Ser	missense	N/A	ENSP00000266086.3	Q9NY91
	SLC5A4-AS1	ENST00000434942.2	TSL:3	n.225-8127_225-8125delTGCinsACT		intron	N/A
	SLC5A4-AS1	ENST00000452181.2	TSL:5	n.274+13687_274+13689delTGCinsACT		intron	N/A

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		2.5

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: chr22-32616950;