chr12-125767-C-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001170738.2(IQSEC3):c.758C>T(p.Pro253Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000481 in 1,512,584 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P253R) has been classified as Uncertain significance.
Frequency
Consequence
NM_001170738.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000348 AC: 53AN: 152178Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000298 AC: 33AN: 110634Hom.: 0 AF XY: 0.000300 AC XY: 18AN XY: 60088
GnomAD4 exome AF: 0.000495 AC: 674AN: 1360406Hom.: 2 Cov.: 30 AF XY: 0.000520 AC XY: 348AN XY: 669712
GnomAD4 genome AF: 0.000348 AC: 53AN: 152178Hom.: 0 Cov.: 33 AF XY: 0.000283 AC XY: 21AN XY: 74328
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.758C>T (p.P253L) alteration is located in exon 3 (coding exon 3) of the IQSEC3 gene. This alteration results from a C to T substitution at nucleotide position 758, causing the proline (P) at amino acid position 253 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