9-137306962-GC-AT

Variant names:

• chr9-137306962-GC-AT
• NM_017820.5:c.2618_2619delGCinsAT
• EXD3 p.Ser873Asn

Variant summary

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

The NM_017820.5(EXD3):​c.2618_2619delGCinsAT​(p.Ser873Asn) 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. S873R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: EXD3 NM_017820.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.210
• Publications: 0 publications found

Genes affected

EXD3 (HGNC:26023): (exonuclease 3'-5' domain containing 3) Predicted to enable 3'-5' exonuclease activity. Predicted to be involved in nucleic acid phosphodiester bond hydrolysis. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017820.5. 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
	EXD3	NM_017820.5	MANE Select	c.2618_2619delGCinsAT	p.Ser873Asn	missense	N/A	NP_060290.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXD3	ENST00000340951.9	TSL:1 MANE Select	c.2618_2619delGCinsAT	p.Ser873Asn	missense	N/A	ENSP00000340474.4	Q8N9H8-1
	EXD3	ENST00000491734.6	TSL:1	n.*1686_*1687delGCinsAT		non_coding_transcript_exon	Exon 15 of 15	ENSP00000435830.1	E9PSB6
	EXD3	ENST00000491734.6	TSL:1	n.*1686_*1687delGCinsAT		3_prime_UTR	Exon 15 of 15	ENSP00000435830.1	E9PSB6

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.21

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: chr9-140201414;