6-138430693-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001144060.2(NHSL1):āc.3652G>Cā(p.Glu1218Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000284 in 1,551,618 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E1218K) has been classified as Uncertain significance.
Frequency
Consequence
NM_001144060.2 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 |
---|---|---|---|---|---|---|---|
NHSL1 | NM_001144060.2 | c.3652G>C | p.Glu1218Gln | missense_variant | 6/8 | ENST00000343505.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NHSL1 | ENST00000343505.10 | c.3652G>C | p.Glu1218Gln | missense_variant | 6/8 | 5 | NM_001144060.2 | P3 | |
NHSL1 | ENST00000427025.6 | c.3664G>C | p.Glu1222Gln | missense_variant | 5/7 | 5 | A2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152202Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000128 AC: 2AN: 156138Hom.: 0 AF XY: 0.0000242 AC XY: 2AN XY: 82792
GnomAD4 exome AF: 0.0000307 AC: 43AN: 1399416Hom.: 0 Cov.: 34 AF XY: 0.0000261 AC XY: 18AN XY: 690224
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152202Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74348
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 02, 2024 | The c.3664G>C (p.E1222Q) alteration is located in exon 5 (coding exon 5) of the NHSL1 gene. This alteration results from a G to C substitution at nucleotide position 3664, causing the glutamic acid (E) at amino acid position 1222 to be replaced by a glutamine (Q). 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