COMMD6 p.Lys57Asn

Variant names:

• chr13-75530150-C-A
• NM_203495.4:c.171G>T
• COMMD6 p.Lys57Asn

Your query was ambiguous. Multiple possible variants found:

• chr13-75530150-C-A
• chr13-75530150-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_203495.4(COMMD6):​c.171G>T​(p.Lys57Asn) 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. 14/21 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: COMMD6 NM_203495.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.601
• Publications: 0 publications found

Genes affected

COMMD6 (HGNC:24015): (COMM domain containing 6) COMMD6 belongs to a family of NF-kappa-B (see RELA; MIM 164014)-inhibiting proteins characterized by the presence of a COMM domain (see COMMD1; MIM 607238) (de Bie et al., 2006 [PubMed 16573520]).[supplied by OMIM, Mar 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12747979).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203495.4. 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
	COMMD6	NM_203495.4	MANE Select	c.171G>T	p.Lys57Asn	missense	Exon 3 of 4	NP_987091.1	Q7Z4G1-1
	COMMD6	NM_203497.4		c.171G>T	p.Lys57Asn	missense	Exon 3 of 5	NP_987093.1	Q7Z4G1-2
	COMMD6	NM_001287392.2		c.90G>T	p.Lys30Asn	missense	Exon 3 of 4	NP_001274321.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COMMD6	ENST00000682242.1	MANE Select	c.171G>T	p.Lys57Asn	missense	Exon 3 of 4	ENSP00000506987.1	Q7Z4G1-1
	COMMD6	ENST00000377619.9	TSL:2	c.216G>T	p.Lys72Asn	missense	Exon 2 of 3	ENSP00000366845.5	B0QZ40
	COMMD6	ENST00000355801.4	TSL:2	c.171G>T	p.Lys57Asn	missense	Exon 3 of 5	ENSP00000348054.4	Q7Z4G1-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.018
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.99	T
PhyloP100		0.60
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.72	N
REVEL	Benign	0.013
Sift	Benign	0.28	T
Sift4G	Benign	0.085	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.062
gMVP		0.15
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr13-76104286;