5-80875315-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002439.5(MSH3):​c.3303-436A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 149,794 control chromosomes in the GnomAD database, including 28,197 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.61 ( 28197 hom., cov: 29)

Consequence

MSH3
NM_002439.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.223
Variant links:
Genes affected
MSH3 (HGNC:7326): (mutS homolog 3) The protein encoded by this gene forms a heterodimer with MSH2 to form MutS beta, part of the post-replicative DNA mismatch repair system. MutS beta initiates mismatch repair by binding to a mismatch and then forming a complex with MutL alpha heterodimer. This gene contains a polymorphic 9 bp tandem repeat sequence in the first exon. The repeat is present 6 times in the reference genome sequence and 3-7 repeats have been reported. Defects in this gene are a cause of susceptibility to endometrial cancer. [provided by RefSeq, Mar 2011]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.681 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MSH3NM_002439.5 linkc.3303-436A>G intron_variant Intron 23 of 23 ENST00000265081.7 NP_002430.3 P20585

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MSH3ENST00000265081.7 linkc.3303-436A>G intron_variant Intron 23 of 23 1 NM_002439.5 ENSP00000265081.6 P20585
MSH3ENST00000658259.1 linkc.3135-436A>G intron_variant Intron 23 of 23 ENSP00000499617.1 A0A590UJW0
MSH3ENST00000667069.1 linkc.3108-436A>G intron_variant Intron 21 of 21 ENSP00000499502.1 A0A590UJN8
MSH3ENST00000670357.1 linkn.*627-436A>G intron_variant Intron 24 of 24 ENSP00000499791.1 A0A590UKC9

Frequencies

GnomAD3 genomes
AF:
0.610
AC:
91348
AN:
149738
Hom.:
28197
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.465
Gnomad AMI
AF:
0.698
Gnomad AMR
AF:
0.577
Gnomad ASJ
AF:
0.560
Gnomad EAS
AF:
0.623
Gnomad SAS
AF:
0.637
Gnomad FIN
AF:
0.728
Gnomad MID
AF:
0.600
Gnomad NFE
AF:
0.686
Gnomad OTH
AF:
0.619
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.610
AC:
91367
AN:
149794
Hom.:
28197
Cov.:
29
AF XY:
0.613
AC XY:
44830
AN XY:
73104
show subpopulations
Gnomad4 AFR
AF:
0.465
Gnomad4 AMR
AF:
0.577
Gnomad4 ASJ
AF:
0.560
Gnomad4 EAS
AF:
0.623
Gnomad4 SAS
AF:
0.638
Gnomad4 FIN
AF:
0.728
Gnomad4 NFE
AF:
0.686
Gnomad4 OTH
AF:
0.619
Alfa
AF:
0.657
Hom.:
41364
Bravo
AF:
0.583

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
1.0
DANN
Benign
0.31

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs33003; hg19: chr5-80171134; API