NM_014186.4:c.70G>C

Variant names:

• chr11-36280819-C-G
• rs201813122
• NM_014186.4:c.70G>C

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_014186.4(COMMD9):​c.70G>C​(p.Val24Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000134 in 1,587,404 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00014 (0 hom.)
• Consequence: COMMD9 NM_014186.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.88
• Publications: 2 publications found

Genes affected

COMMD9 (HGNC:25014): (COMM domain containing 9) Predicted to be involved in sodium ion transport. Predicted to act upstream of or within cholesterol homeostasis. Located in Golgi apparatus; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.34806508).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014186.4. 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
	COMMD9	NM_014186.4	MANE Select	c.70G>C	p.Val24Leu	missense	Exon 2 of 6	NP_054905.2	Q53FR9
	COMMD9	NM_001307937.2		c.43G>C	p.Val15Leu	missense	Exon 3 of 7	NP_001294866.1
	COMMD9	NM_001307932.2		c.70G>C	p.Val24Leu	missense	Exon 2 of 5	NP_001294861.1	E9PJ95

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COMMD9	ENST00000263401.10	TSL:1 MANE Select	c.70G>C	p.Val24Leu	missense	Exon 2 of 6	ENSP00000263401.5	Q9P000-1
	COMMD9	ENST00000877672.1		c.70G>C	p.Val24Leu	missense	Exon 2 of 6	ENSP00000547731.1
	COMMD9	ENST00000532705.1	TSL:2	c.70G>C	p.Val24Leu	missense	Exon 2 of 5	ENSP00000435599.1	E9PJ95

Frequencies

GnomAD3 genomes AF: 0.000106 AC: 16 AN: 151526 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000485

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000764 AC: 18 AN: 235578 AF XY: 0.0000784

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000156

Gnomad OTH exome AF: 0.000175

GnomAD4 exome AF: 0.000137 AC: 196 AN: 1435878 Hom.: 0 Cov.: 31 AF XY: 0.000121 AC XY: 86 AN XY: 713002

African (AFR) AF: 0.00 AC: 0 AN: 32340

American (AMR) AF: 0.00 AC: 0 AN: 40654

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25228

East Asian (EAS) AF: 0.00 AC: 0 AN: 39158

South Asian (SAS) AF: 0.00 AC: 0 AN: 82642

European-Finnish (FIN) AF: 0.0000189 AC: 1 AN: 52794

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5652

European-Non Finnish (NFE) AF: 0.000168 AC: 185 AN: 1098342

Other (OTH) AF: 0.000169 AC: 10 AN: 59068

GnomAD4 genome AF: 0.000106 AC: 16 AN: 151526 Hom.: 0 Cov.: 33 AF XY: 0.0000811 AC XY: 6 AN XY: 73956

African (AFR) AF: 0.0000485 AC: 2 AN: 41208

American (AMR) AF: 0.00 AC: 0 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5142

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10452

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 67912

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.000151 Hom.: 0

Bravo AF: 0.0000642

ExAC AF: 0.000107 AC: 13

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.028
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		3.9
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.087
Sift	Benign	0.092	T
Sift4G	Benign	0.14	T
Polyphen		0.067	B
Vest4		0.62
MVP		0.15
MPC		0.28
ClinPred		0.15	T
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.54
gMVP		0.57
Mutation Taster		=62/38	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: rs201813122; hg19: chr11-36302369;