chr5-116091122-C-A

Variant names:

• chr5-116091122-C-A
• rs146111323
• NM_016144.4:c.176C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016144.4(COMMD10):​c.176C>A​(p.Ala59Glu) 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. 16/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. A59V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: COMMD10 NM_016144.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.428
• Publications: 3 publications found

Genes affected

COMMD10 (HGNC:30201): (COMM domain containing 10) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03264928).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016144.4. 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
	COMMD10	NM_016144.4	MANE Select	c.176C>A	p.Ala59Glu	missense	Exon 3 of 7	NP_057228.1	Q9Y6G5
	COMMD10	NM_001308080.2		c.134C>A	p.Ala45Glu	missense	Exon 3 of 7	NP_001295009.1	D6RJ90
	COMMD10	NR_146218.2		n.204C>A		non_coding_transcript_exon	Exon 3 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COMMD10	ENST00000274458.9	TSL:1 MANE Select	c.176C>A	p.Ala59Glu	missense	Exon 3 of 7	ENSP00000274458.4	Q9Y6G5
	COMMD10	ENST00000632434.1	TSL:1	c.134C>A	p.Ala45Glu	missense	Exon 3 of 7	ENSP00000488332.1	D6RJ90
	COMMD10	ENST00000515539.5	TSL:3	c.134C>A	p.Ala45Glu	missense	Exon 3 of 7	ENSP00000427319.1	D6RJ90

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	10
DANN	Benign	0.40
DEOGEN2	Benign	0.0080	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.27	N
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.033	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.90	L
PhyloP100		0.43
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.077
Sift	Benign	0.65	T
Sift4G	Benign	1.0	T
Polyphen		0.0060	B
Vest4		0.34
MutPred		0.47		Gain of helix (P = 0.0325)
MVP		0.048
MPC		0.0057
ClinPred		0.079	T
GERP RS		1.8
PromoterAI		-0.041	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.051
gMVP		0.34
Mutation Taster		=88/12	polymorphism

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: rs146111323; hg19: chr5-115426819;