chr22-32231073-T-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_014227.3(SLC5A4):c.1024A>T(p.Met342Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_014227.3 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC5A4 | NM_014227.3 | c.1024A>T | p.Met342Leu | missense_variant, splice_region_variant | 10/15 | ENST00000266086.6 | |
SLC5A4-AS1 | NR_149072.1 | n.274+23797T>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC5A4 | ENST00000266086.6 | c.1024A>T | p.Met342Leu | missense_variant, splice_region_variant | 10/15 | 1 | NM_014227.3 | P1 | |
SLC5A4-AS1 | ENST00000452181.2 | n.274+23797T>A | intron_variant, non_coding_transcript_variant | 5 | |||||
SLC5A4-AS1 | ENST00000434942.2 | n.507+1701T>A | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250910Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135586
GnomAD4 exome AF: 6.87e-7 AC: 1AN: 1455016Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0AN XY: 724402
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 03, 2023 | The c.1024A>T (p.M342L) alteration is located in exon 10 (coding exon 10) of the SLC5A4 gene. This alteration results from a A to T substitution at nucleotide position 1024, causing the methionine (M) at amino acid position 342 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at