chr6-122804919-T-C
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_006714.5(SMPDL3A):c.749T>C(p.Ile250Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000559 in 1,611,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_006714.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SMPDL3A | ENST00000368440.5 | c.749T>C | p.Ile250Thr | missense_variant | Exon 6 of 8 | 1 | NM_006714.5 | ENSP00000357425.4 | ||
SMPDL3A | ENST00000539041.5 | c.356T>C | p.Ile119Thr | missense_variant | Exon 5 of 7 | 2 | ENSP00000442152.1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152212Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000803 AC: 2AN: 249218Hom.: 0 AF XY: 0.00000742 AC XY: 1AN XY: 134778
GnomAD4 exome AF: 0.00000411 AC: 6AN: 1458978Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 2AN XY: 725532
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152212Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74364
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.749T>C (p.I250T) alteration is located in exon 6 (coding exon 6) of the SMPDL3A gene. This alteration results from a T to C substitution at nucleotide position 749, causing the isoleucine (I) at amino acid position 250 to be replaced by a threonine (T). 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