rs121908936
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 9P and 1B. PVS1PP5BS2_Supporting
The NM_002299.4(LCT):c.4170T>A(p.Tyr1390Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000311 in 1,613,974 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_002299.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LCT | NM_002299.4 | c.4170T>A | p.Tyr1390Ter | stop_gained | 9/17 | ENST00000264162.7 | |
LCT | XM_017004088.3 | c.4170T>A | p.Tyr1390Ter | stop_gained | 9/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LCT | ENST00000264162.7 | c.4170T>A | p.Tyr1390Ter | stop_gained | 9/17 | 1 | NM_002299.4 | P1 | |
LCT | ENST00000452974.1 | c.2466T>A | p.Tyr822Ter | stop_gained, NMD_transcript_variant | 3/7 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.000690 AC: 105AN: 152146Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000872 AC: 219AN: 251102Hom.: 1 AF XY: 0.000913 AC XY: 124AN XY: 135774
GnomAD4 exome AF: 0.000272 AC: 397AN: 1461828Hom.: 2 Cov.: 33 AF XY: 0.000287 AC XY: 209AN XY: 727220
GnomAD4 genome ? AF: 0.000690 AC: 105AN: 152146Hom.: 0 Cov.: 33 AF XY: 0.00116 AC XY: 86AN XY: 74310
ClinVar
Submissions by phenotype
Congenital lactase deficiency Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 01, 2006 | - - |
Pathogenic, no assertion criteria provided | curation | Reproductive Health Research and Development, BGI Genomics | Jan 06, 2020 | NM_002299.2:c.4170T>A in the LCT gene has an allele frequency of 0.01 in European (Finnish) subpopulation in the gnomAD database. Twenty-seven patients out of 32 (84%) affected with congenital lactase deficiency were homozygous for this nonsense mutation, c.4170T>A (p.Y1390X) (PMID: 16400612). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Taken together, we interprete this variant as Pathogenic/Likely pathogenic. ACMG/AMP Criteria applied: PVS1; PS4. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at