12-25123241-T-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_018272.5(DNAI7):c.1048A>T(p.Met350Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000747 in 1,606,304 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 (★).
Frequency
Consequence
NM_018272.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAI7 | NM_018272.5 | c.1048A>T | p.Met350Leu | missense_variant | 10/16 | ENST00000395987.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAI7 | ENST00000395987.8 | c.1048A>T | p.Met350Leu | missense_variant | 10/16 | 1 | NM_018272.5 | A1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152208Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000451 AC: 11AN: 243894Hom.: 0 AF XY: 0.0000455 AC XY: 6AN XY: 131968
GnomAD4 exome AF: 0.00000756 AC: 11AN: 1454096Hom.: 0 Cov.: 28 AF XY: 0.00000691 AC XY: 5AN XY: 723374
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152208Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74364
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 08, 2023 | The c.1048A>T (p.M350L) alteration is located in exon 10 (coding exon 10) of the CASC1 gene. This alteration results from a A to T substitution at nucleotide position 1048, causing the methionine (M) at amino acid position 350 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