COMMD3 p.His142Gln

Variant names:

• chr10-22318820-T-A
• NM_012071.4:c.426T>A
• COMMD3 p.His142Gln

Your query was ambiguous. Multiple possible variants found:

• chr10-22318820-T-A
• chr10-22318820-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_012071.4(COMMD3):​c.426T>A​(p.His142Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/25 in silico tools predict a benign outcome for this variant. 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 Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: COMMD3 NM_012071.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.59
• Publications: 0 publications found

Genes affected

COMMD3 (HGNC:23332): (COMM domain containing 3) Predicted to be involved in sodium ion transport. Predicted to be located in extracellular region and ficolin-1-rich granule lumen. [provided by Alliance of Genome Resources, Apr 2022]

COMMD3-BMI1 (HGNC:48326): (COMMD3-BMI1 readthrough) This locus represents naturally occurring read-through transcription between the neighboring COMM domain-containing protein 3 and polycomb complex protein BMI-1 genes on chromosome 10. The read-through transcript produces a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Feb 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012071.4. 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
	COMMD3	NM_012071.4	MANE Select	c.426T>A	p.His142Gln	missense	Exon 6 of 8	NP_036203.1	Q9UBI1
	COMMD3-BMI1	NM_001204062.2		c.351-139T>A		intron	N/A	NP_001190991.1	R4GMX3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COMMD3	ENST00000376836.8	TSL:1 MANE Select	c.426T>A	p.His142Gln	missense	Exon 6 of 8	ENSP00000366032.3	Q9UBI1
	COMMD3-BMI1	ENST00000602390.5	TSL:2	c.351-139T>A		intron	N/A	ENSP00000473391.1	R4GMX3
	COMMD3	ENST00000602574.5	TSL:1	n.804T>A		non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	22
DANN	Benign	0.94
DEOGEN2	Benign	0.012	T
Eigen	Benign	0.15
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.6
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.087
Sift	Benign	0.11	T
Sift4G	Benign	0.19	T
Varity_R		0.096
gMVP		0.22
Mutation Taster		=70/30	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.26		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.26		Position offset: -14
DS_DG_spliceai		0.24		Position offset: 42

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: chr10-22607749;