2-62135936-A-T

Variant names:

• chr2-62135936-A-T
• rs147438507
• NM_152516.4:c.568A>T

Variant summary

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

The NM_152516.4(COMMD1):​c.568A>T​(p.Asn190Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000724 in 1,381,412 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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. N190D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: COMMD1 NM_152516.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.340
• Publications: 1 publications found

Genes affected

COMMD1 (HGNC:23024): (copper metabolism domain containing 1) Enables several functions, including phosphatidylinositol-3,4-bisphosphate binding activity; phospholipid binding activity; and protein homodimerization activity. Involved in several processes, including Golgi to plasma membrane transport; negative regulation of protein localization to cell surface; and regulation of cellular protein metabolic process. Acts upstream of or within negative regulation of NF-kappaB transcription factor activity. Located in cytosol; endosome; and nucleoplasm. Part of Cul2-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000229839 (HGNC:):

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=0.1331957).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152516.4. 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
	COMMD1	NM_152516.4	MANE Select	c.568A>T	p.Asn190Tyr	missense	Exon 3 of 3	NP_689729.1	Q8N668-1
	COMMD1	NM_001321781.3		c.370A>T	p.Asn124Tyr	missense	Exon 3 of 3	NP_001308710.1
	COMMD1	NM_001321782.3		c.370A>T	p.Asn124Tyr	missense	Exon 3 of 3	NP_001308711.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COMMD1	ENST00000311832.6	TSL:1 MANE Select	c.568A>T	p.Asn190Tyr	missense	Exon 3 of 3	ENSP00000308236.5	Q8N668-1
	ENSG00000229839	ENST00000425966.6	TSL:1	n.308+1613T>A		intron	N/A
	COMMD1	ENST00000897153.1		c.661A>T	p.Asn221Tyr	missense	Exon 4 of 4	ENSP00000567212.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.24e-7 AC: 1 AN: 1381412 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 692194

African (AFR) AF: 0.00 AC: 0 AN: 31850

American (AMR) AF: 0.00 AC: 0 AN: 44634

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25666

East Asian (EAS) AF: 0.00 AC: 0 AN: 39318

South Asian (SAS) AF: 0.00 AC: 0 AN: 84760

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53294

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5612

European-Non Finnish (NFE) AF: 9.63e-7 AC: 1 AN: 1038530

Other (OTH) AF: 0.00 AC: 0 AN: 57748

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.085	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.080	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.090
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.34
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.42	N
REVEL	Benign	0.058
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.21	B
Vest4		0.17
MutPred		0.38		Gain of catalytic residue at L185 (P = 0.0629)
MVP		0.57
MPC		0.81
ClinPred		0.53	D
GERP RS		3.2
PromoterAI		0.00030	Neutral
Varity_R		0.11
gMVP		0.39
Mutation Taster		=76/24	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: rs147438507; hg19: chr2-62363071;