chr1-75797088-C-A
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_002440.4(MSH4):c.103C>A(p.Leu35Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000424 in 1,614,058 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_002440.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MSH4 | NM_002440.4 | c.103C>A | p.Leu35Ile | missense_variant | 1/20 | ENST00000263187.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MSH4 | ENST00000263187.4 | c.103C>A | p.Leu35Ile | missense_variant | 1/20 | 1 | NM_002440.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000703 AC: 107AN: 152220Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000551 AC: 138AN: 250652Hom.: 0 AF XY: 0.000523 AC XY: 71AN XY: 135640
GnomAD4 exome AF: 0.000395 AC: 577AN: 1461720Hom.: 2 Cov.: 31 AF XY: 0.000407 AC XY: 296AN XY: 727138
GnomAD4 genome ? AF: 0.000709 AC: 108AN: 152338Hom.: 0 Cov.: 32 AF XY: 0.000738 AC XY: 55AN XY: 74492
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 21, 2022 | The c.103C>A (p.L35I) alteration is located in exon 1 (coding exon 1) of the MSH4 gene. This alteration results from a C to A substitution at nucleotide position 103, causing the leucine (L) at amino acid position 35 to be replaced by an isoleucine (I). 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