rs3797897

Variant names:

• chr5-80824711-C-G
• rs3797897
• NM_002439.5:c.2813+10970C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002439.5(MSH3):​c.2813+10970C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0807 in 152,256 control chromosomes in the GnomAD database, including 893 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 0.081 (893 hom., cov: 32)
• Consequence: MSH3 NM_002439.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.867
• Publications: 2 publications found

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]

MSH3 Gene-Disease associations (from GenCC):

• familial adenomatous polyposis 4

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• MSH3-related attenuated familial adenomatous polyposis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Lynch syndrome

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002439.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSH3	NM_002439.5	MANE Select	c.2813+10970C>G		intron	N/A	NP_002430.3	P20585

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSH3	ENST00000265081.7	TSL:1 MANE Select	c.2813+10970C>G		intron	N/A	ENSP00000265081.6	P20585
	MSH3	ENST00000658259.1		c.2645+10970C>G		intron	N/A	ENSP00000499617.1	A0A590UJW0
	MSH3	ENST00000667069.1		c.2618+10970C>G		intron	N/A	ENSP00000499502.1	A0A590UJN8

Frequencies

GnomAD3 genomes AF: 0.0808 AC: 12287 AN: 152138 Hom.: 893 Cov.: 32

Gnomad AFR AF: 0.0273

Gnomad AMI AF: 0.0991

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.0721

Gnomad FIN AF: 0.0697

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0706

Gnomad OTH AF: 0.0774

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0807 AC: 12291 AN: 152256 Hom.: 893 Cov.: 32 AF XY: 0.0841 AC XY: 6260 AN XY: 74452

African (AFR) AF: 0.0272 AC: 1129 AN: 41550

American (AMR) AF: 0.191 AC: 2923 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 382 AN: 3468

East Asian (EAS) AF: 0.328 AC: 1700 AN: 5178

South Asian (SAS) AF: 0.0724 AC: 349 AN: 4822

European-Finnish (FIN) AF: 0.0697 AC: 740 AN: 10618

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0706 AC: 4799 AN: 68010

Other (OTH) AF: 0.0785 AC: 166 AN: 2114

Alfa AF: 0.0812 Hom.: 96

Bravo AF: 0.0951

Asia WGS AF: 0.158 AC: 550 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.46
DANN	Benign	0.74
PhyloP100		-0.87
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3797897; hg19: chr5-80120530;