rs149125057

Variant names:

• chr13-75530224-C-T
• rs149125057
• NM_203495.4:c.97G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_203495.4(COMMD6):​c.97G>A​(p.Asp33Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000527 in 1,613,598 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000053 (0 hom.)
• Consequence: COMMD6 NM_203495.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.64
• 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.30752027).

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.97G>A	p.Asp33Asn	missense	Exon 3 of 4	NP_987091.1	Q7Z4G1-1
	COMMD6	NM_203497.4		c.97G>A	p.Asp33Asn	missense	Exon 3 of 5	NP_987093.1	Q7Z4G1-2
	COMMD6	NM_001287392.2		c.16G>A	p.Asp6Asn	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.97G>A	p.Asp33Asn	missense	Exon 3 of 4	ENSP00000506987.1	Q7Z4G1-1
	COMMD6	ENST00000377619.9	TSL:2	c.142G>A	p.Asp48Asn	missense	Exon 2 of 3	ENSP00000366845.5	B0QZ40
	COMMD6	ENST00000355801.4	TSL:2	c.97G>A	p.Asp33Asn	missense	Exon 3 of 5	ENSP00000348054.4	Q7Z4G1-2

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152180 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000637 AC: 16 AN: 251048 AF XY: 0.0000589

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000880

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000534 AC: 78 AN: 1461418 Hom.: 0 Cov.: 29 AF XY: 0.0000413 AC XY: 30 AN XY: 727018

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.000134 AC: 6 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.00 AC: 0 AN: 86196

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53386

Middle Eastern (MID) AF: 0.000869 AC: 5 AN: 5756

European-Non Finnish (NFE) AF: 0.0000567 AC: 63 AN: 1111772

Other (OTH) AF: 0.0000662 AC: 4 AN: 60378

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152180 Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4 AN XY: 74346

African (AFR) AF: 0.0000483 AC: 2 AN: 41442

American (AMR) AF: 0.0000654 AC: 1 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68038

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.000135 Hom.: 0

Bravo AF: 0.0000982

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000659 AC: 8

EpiCase AF: 0.0000546

EpiControl AF: 0.000119

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	0.17
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.65
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.034	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-1.1	T
PhyloP100		4.6
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.19
Sift	Benign	0.32	T
Sift4G	Benign	0.31	T
Polyphen		1.0	D
Vest4		0.30
MVP		0.27
MPC		0.12
ClinPred		0.82	D
GERP RS		5.1
Varity_R		0.25
gMVP		0.32
Mutation Taster		=49/51	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs149125057; hg19: chr13-76104360;