chr11-36280819-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014186.4(COMMD9):​c.70G>A​(p.Val24Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000139 in 1,435,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. V24L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: COMMD9 NM_014186.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.88

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23923174).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COMMD9	NM_014186.4	c.70G>A	p.Val24Ile	missense_variant	Exon 2 of 6	ENST00000263401.10	NP_054905.2
COMMD9	NM_001307937.2	c.43G>A	p.Val15Ile	missense_variant	Exon 3 of 7		NP_001294866.1
COMMD9	NM_001307932.2	c.70G>A	p.Val24Ile	missense_variant	Exon 2 of 5		NP_001294861.1
COMMD9	NM_001101653.2	c.52-2203G>A		intron_variant	Intron 1 of 4		NP_001095123.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COMMD9	ENST00000263401.10	c.70G>A	p.Val24Ile	missense_variant	Exon 2 of 6	1	NM_014186.4	ENSP00000263401.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1435878 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 713002

Gnomad4 AFR exome AF: 0.0000618

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.016	T;T
Eigen	Benign	0.066
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.77	T;T
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.45	N;N
REVEL	Benign	0.12
Sift	Benign	0.070	T;D
Sift4G	Uncertain	0.028	D;D
Polyphen		0.0030	B;.
Vest4		0.28
MutPred		0.59		Loss of ubiquitination at K21 (P = 0.0768);Loss of ubiquitination at K21 (P = 0.0768);
MVP		0.12
MPC		0.24
ClinPred		0.65	D
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.24
gMVP		0.28

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

Publications

LitVar

Other links and lift over

dbSNP: rs201813122; hg19: chr11-36302369;