rs759519874

Variant names:

• chr11-36278592-T-A
• rs759519874
• NM_014186.4:c.202A>T

Your query was ambiguous. Multiple possible variants found:

• chr11-36278592-T-A
• chr11-36278592-T-C

Variant summary

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

The NM_014186.4(COMMD9):​c.202A>T​(p.Thr68Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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. T68A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: COMMD9 NM_014186.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.18

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=0.16154563).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COMMD9	NM_014186.4	c.202A>T	p.Thr68Ser	missense_variant	Exon 3 of 6	ENST00000263401.10	NP_054905.2
COMMD9	NM_001307937.2	c.175A>T	p.Thr59Ser	missense_variant	Exon 4 of 7		NP_001294866.1
COMMD9	NM_001307932.2	c.202A>T	p.Thr68Ser	missense_variant	Exon 3 of 5		NP_001294861.1
COMMD9	NM_001101653.2	c.76A>T	p.Thr26Ser	missense_variant	Exon 2 of 5		NP_001095123.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COMMD9	ENST00000263401.10	c.202A>T	p.Thr68Ser	missense_variant	Exon 3 of 6	1	NM_014186.4	ENSP00000263401.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	18
DANN	Benign	0.93
DEOGEN2	Benign	0.0084	T;.;T
Eigen	Benign	-0.030
Eigen_PC	Benign	0.16
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.75	T;T;T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.16	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.86	L;.;.
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.67	N;N;N
REVEL	Benign	0.086
Sift	Benign	0.58	T;T;T
Sift4G	Benign	0.57	T;T;T
Polyphen		0.052	B;B;.
Vest4		0.23
MutPred		0.61		Gain of phosphorylation at T68 (P = 0.0546);.;Gain of phosphorylation at T68 (P = 0.0546);
MVP		0.082
MPC		0.37
ClinPred		0.45	T
GERP RS		5.8
Varity_R		0.37
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs759519874; hg19: chr11-36300142;