2-47806284-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_000179.3(MSH6):āc.3727A>Gā(p.Thr1243Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T1243S) has been classified as Likely benign.
Frequency
Consequence
NM_000179.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251210Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135762
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461760Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727192
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Endometrial carcinoma Uncertain:2
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ACMG classification criteria: PM2 supporting -
Hereditary cancer-predisposing syndrome Uncertain:1
The c.3727A>G (p.T1243A) alteration is located in exon 8 (coding exon 8) of the MSH6 gene. This alteration results from a A to G substitution at nucleotide position 3727, causing the threonine (T) at amino acid position 1243 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Hereditary nonpolyposis colorectal neoplasms Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at