1-241866849-AT-GC

Variant names:

• chr1-241866849-AT-GC
• NM_130398.4:c.1061_1062delATinsGC
• EXO1 p.His354Arg

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_130398.4(EXO1):​c.1061_1062delATinsGC​(p.His354Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EXO1 NM_130398.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.399
• Publications: 0 publications found

Genes affected

EXO1 (HGNC:3511): (exonuclease 1) This gene encodes a protein with 5' to 3' exonuclease activity as well as an RNase H activity. It is similar to the Saccharomyces cerevisiae protein Exo1 which interacts with Msh2 and which is involved in mismatch repair and recombination. Alternative splicing of this gene results in three transcript variants encoding two different isoforms. [provided by RefSeq, Jul 2008]

EXO1 Gene-Disease associations (from GenCC):

• Lynch syndrome

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130398.4. 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
	EXO1	NM_130398.4	MANE Select	c.1061_1062delATinsGC	p.His354Arg	missense	N/A	NP_569082.2	Q9UQ84-1
	EXO1	NM_006027.4		c.1061_1062delATinsGC	p.His354Arg	missense	N/A	NP_006018.4	Q9UQ84-1
	EXO1	NM_001319224.2		c.1061_1062delATinsGC	p.His354Arg	missense	N/A	NP_001306153.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXO1	ENST00000366548.8	TSL:1 MANE Select	c.1061_1062delATinsGC	p.His354Arg	missense	N/A	ENSP00000355506.3	Q9UQ84-1
	EXO1	ENST00000348581.9	TSL:1	c.1061_1062delATinsGC	p.His354Arg	missense	N/A	ENSP00000311873.5	Q9UQ84-1
	EXO1	ENST00000518483.5	TSL:1	c.1061_1062delATinsGC	p.His354Arg	missense	N/A	ENSP00000430251.1	Q9UQ84-4

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.40

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-242030151;