6-109443020-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_003080.3(SMPD2):āc.668T>Cā(p.Val223Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,614,234 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V223I) has been classified as Likely benign.
Frequency
Consequence
NM_003080.3 missense
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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SMPD2 | NM_003080.3 | c.668T>C | p.Val223Ala | missense_variant | 8/10 | ENST00000258052.8 | NP_003071.2 | |
SMPD2 | XM_011536079.2 | c.353T>C | p.Val118Ala | missense_variant | 6/8 | XP_011534381.1 | ||
SMPD2 | XR_942566.3 | n.1066T>C | non_coding_transcript_exon_variant | 8/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SMPD2 | ENST00000258052.8 | c.668T>C | p.Val223Ala | missense_variant | 8/10 | 1 | NM_003080.3 | ENSP00000258052.3 | ||
SMPD2 | ENST00000458487.1 | c.356T>C | p.Val119Ala | missense_variant | 2/4 | 2 | ENSP00000399731.1 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152238Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251336Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135854
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461878Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3AN XY: 727240
GnomAD4 genome AF: 0.0000722 AC: 11AN: 152356Hom.: 0 Cov.: 33 AF XY: 0.0000805 AC XY: 6AN XY: 74504
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 21, 2023 | The c.668T>C (p.V223A) alteration is located in exon 8 (coding exon 8) of the SMPD2 gene. This alteration results from a T to C substitution at nucleotide position 668, causing the valine (V) at amino acid position 223 to be replaced by an alanine (A). 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