11-36280819-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_014186.4(COMMD9):​c.70G>T​(p.Val24Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000696 in 1,435,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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: 7.0e-7 (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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.82

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COMMD9	NM_014186.4	c.70G>T	p.Val24Phe	missense_variant	Exon 2 of 6	ENST00000263401.10	NP_054905.2
COMMD9	NM_001307937.2	c.43G>T	p.Val15Phe	missense_variant	Exon 3 of 7		NP_001294866.1
COMMD9	NM_001307932.2	c.70G>T	p.Val24Phe	missense_variant	Exon 2 of 5		NP_001294861.1
COMMD9	NM_001101653.2	c.52-2203G>T		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>T	p.Val24Phe	missense_variant	Exon 2 of 6	1	NM_014186.4	ENSP00000263401.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.96e-7 AC: 1 AN: 1435876 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 713002

Gnomad4 AFR exome AF: 0.00

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: 9.10e-7

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	Pathogenic	0.75
BayesDel_addAF	Benign	-0.042	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.063	T;T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.029	D
MetaRNN	Pathogenic	0.82	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	M;.
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-3.0	D;D
REVEL	Benign	0.21
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0050	D;D
Polyphen		0.78	P;.
Vest4		0.85
MutPred		0.76		Loss of ubiquitination at K21 (P = 0.1306);Loss of ubiquitination at K21 (P = 0.1306);
MVP		0.17
MPC		0.84
ClinPred		0.97	D
GERP RS		3.8
Varity_R		0.89
gMVP		0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-36302369;