chr7-44517235-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_001101648.2(NPC1L1):c.3259G>T(p.Asp1087Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000434 in 1,613,838 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. D1087E) has been classified as Uncertain significance.
Frequency
Consequence
NM_001101648.2 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 | UniProt |
---|---|---|---|---|---|---|---|
NPC1L1 | NM_001101648.2 | c.3259G>T | p.Asp1087Tyr | missense_variant | 15/19 | ENST00000381160.8 | |
NPC1L1 | NM_013389.3 | c.3340G>T | p.Asp1114Tyr | missense_variant | 16/20 | ||
NPC1L1 | XM_011515326.4 | c.3064G>T | p.Asp1022Tyr | missense_variant | 14/18 | ||
NPC1L1 | XM_011515328.3 | c.1618G>T | p.Asp540Tyr | missense_variant | 12/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NPC1L1 | ENST00000381160.8 | c.3259G>T | p.Asp1087Tyr | missense_variant | 15/19 | 1 | NM_001101648.2 | P1 | |
NPC1L1 | ENST00000289547.8 | c.3340G>T | p.Asp1114Tyr | missense_variant | 16/20 | 1 | |||
NPC1L1 | ENST00000546276.5 | c.3121G>T | p.Asp1041Tyr | missense_variant | 14/18 | 1 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 151984Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000636 AC: 16AN: 251424Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135880
GnomAD4 exome AF: 0.0000424 AC: 62AN: 1461854Hom.: 0 Cov.: 32 AF XY: 0.0000385 AC XY: 28AN XY: 727216
GnomAD4 genome AF: 0.0000526 AC: 8AN: 151984Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74232
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 30, 2023 | The c.3340G>T (p.D1114Y) alteration is located in exon 16 (coding exon 16) of the NPC1L1 gene. This alteration results from a G to T substitution at nucleotide position 3340, causing the aspartic acid (D) at amino acid position 1114 to be replaced by a tyrosine (Y). 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