14-75046806-A-G
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_001040108.2(MLH3):c.2850T>C(p.Asn950Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,814 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
MLH3
NM_001040108.2 synonymous
NM_001040108.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.114
Publications
0 publications found
Genes affected
MLH3 (HGNC:7128): (mutL homolog 3) This gene is a member of the MutL-homolog (MLH) family of DNA mismatch repair (MMR) genes. MLH genes are implicated in maintaining genomic integrity during DNA replication and after meiotic recombination. The protein encoded by this gene functions as a heterodimer with other family members. Somatic mutations in this gene frequently occur in tumors exhibiting microsatellite instability, and germline mutations have been linked to hereditary nonpolyposis colorectal cancer type 7 (HNPCC7). Several alternatively spliced transcript variants have been identified, but the full-length nature of only two transcript variants has been determined. [provided by RefSeq, Jul 2008]
MLH3 Gene-Disease associations (from GenCC):
- colorectal cancer, hereditary nonpolyposis, type 7Inheritance: AD, AR Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, ClinGen, Laboratory for Molecular Medicine
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (REVEL=0.014).
BP6
Variant 14-75046806-A-G is Benign according to our data. Variant chr14-75046806-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3232499.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.114 with no splicing effect.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001040108.2. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| MLH3 | NM_001040108.2 | MANE Select | c.2850T>C | p.Asn950Asn | synonymous | Exon 2 of 13 | NP_001035197.1 | ||
| MLH3 | NM_014381.3 | c.2850T>C | p.Asn950Asn | synonymous | Exon 2 of 12 | NP_055196.2 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| MLH3 | ENST00000355774.7 | TSL:5 MANE Select | c.2850T>C | p.Asn950Asn | synonymous | Exon 2 of 13 | ENSP00000348020.2 | ||
| MLH3 | ENST00000380968.6 | TSL:1 | c.2850T>C | p.Asn950Asn | synonymous | Exon 2 of 12 | ENSP00000370355.3 | ||
| MLH3 | ENST00000556257.5 | TSL:5 | c.2850T>C | p.Asn950Asn | synonymous | Exon 2 of 7 | ENSP00000451540.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461814Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1AN XY: 727198 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1461814
Hom.:
Cov.:
34
AF XY:
AC XY:
1
AN XY:
727198
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33480
American (AMR)
AF:
AC:
0
AN:
44722
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26134
East Asian (EAS)
AF:
AC:
0
AN:
39690
South Asian (SAS)
AF:
AC:
0
AN:
86252
European-Finnish (FIN)
AF:
AC:
0
AN:
53410
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1111966
Other (OTH)
AF:
AC:
0
AN:
60392
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
ClinVar submissions as Germline
Significance:Likely benign
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
-
1
not specified (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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