rs1279553139

Variant names:

• chr11-36276223-C-T
• rs1279553139
• NM_014186.4:c.370G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-36276223-C-T
• chr11-36276223-C-A

Variant summary

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

The NM_014186.4(COMMD9):​c.370G>A​(p.Val124Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: COMMD9 NM_014186.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.40
• Publications: 1 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: 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_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.370G>A	p.Val124Ile	missense	Exon 5 of 6	NP_054905.2	Q53FR9
	COMMD9	NM_001307937.2		c.343G>A	p.Val115Ile	missense	Exon 6 of 7	NP_001294866.1
	COMMD9	NM_001307932.2		c.335G>A	p.Gly112Asp	missense	Exon 4 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.370G>A	p.Val124Ile	missense	Exon 5 of 6	ENSP00000263401.5	Q9P000-1
	COMMD9	ENST00000877672.1		c.391G>A	p.Val131Ile	missense	Exon 5 of 6	ENSP00000547731.1
	COMMD9	ENST00000532705.1	TSL:2	c.335G>A	p.Gly112Asp	missense	Exon 4 of 5	ENSP00000435599.1	E9PJ95

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000312 Hom.: 0

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	Benign	0.080
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Benign	-0.48
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0089	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.010	T
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-1.1	T
PhyloP100		3.4
PROVEAN	Benign	-0.44	N
REVEL	Benign	0.059
Sift	Benign	0.80	T
Sift4G	Benign	0.43	T
Vest4		0.65
MutPred		0.13		Gain of solvent accessibility (P = 0.0638)
MVP		0.63
ClinPred		0.86	D
GERP RS		4.8
Varity_R		0.17
Mutation Taster		=81/19	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: rs1279553139; hg19: chr11-36297773;