11-36276223-C-T

Position:

• chr11-36276223-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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. 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

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COMMD9	NM_014186.4	c.370G>A	p.Val124Ile	missense_variant	5/6	ENST00000263401.10	NP_054905.2
COMMD9	NM_001307937.2	c.343G>A	p.Val115Ile	missense_variant	6/7		NP_001294866.1
COMMD9	NM_001307932.2	c.335G>A	p.Gly112Asp	missense_variant	4/5		NP_001294861.1
COMMD9	NM_001101653.2	c.244G>A	p.Val82Ile	missense_variant	4/5		NP_001095123.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COMMD9	ENST00000263401.10	c.370G>A	p.Val124Ile	missense_variant	5/6	1	NM_014186.4	ENSP00000263401	P1
COMMD9	ENST00000532705.1	c.335G>A	p.Gly112Asp	missense_variant	4/5	2		ENSP00000435599
COMMD9	ENST00000452374.6	c.244G>A	p.Val82Ile	missense_variant	4/5	2		ENSP00000392510
COMMD9	ENST00000533643.1	n.194G>A		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000312 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2021

The c.370G>A (p.V124I) alteration is located in exon 5 (coding exon 5) of the COMMD9 gene. This alteration results from a G to A substitution at nucleotide position 370, causing the valine (V) at amino acid position 124 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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
MutationTaster	Benign	1.0	D;D;N
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

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: rs1279553139; hg19: chr11-36297773;