5-116085056-G-C

Variant names:

• chr5-116085056-G-C
• NM_016144.4:c.4G>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 PM2

The NM_016144.4(COMMD10):​c.4G>C​(p.Ala2Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: COMMD10 NM_016144.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.32

Genes affected

COMMD10 (HGNC:30201): (COMM domain containing 10) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000271918 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM1: In a modified_residue N-acetylalanine (size 0) in uniprot entity COMDA_HUMAN
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COMMD10	NM_016144.4	c.4G>C	p.Ala2Pro	missense_variant	Exon 1 of 7	ENST00000274458.9	NP_057228.1
COMMD10	NR_146218.2	n.32G>C		non_coding_transcript_exon_variant	Exon 1 of 7
COMMD10	NR_146220.2	n.32G>C		non_coding_transcript_exon_variant	Exon 1 of 8
COMMD10	NR_146219.2	n.-222G>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COMMD10	ENST00000274458.9	c.4G>C	p.Ala2Pro	missense_variant	Exon 1 of 7	1	NM_016144.4	ENSP00000274458.4
COMMD10	ENST00000632434	c.-39G>C		5_prime_UTR_variant	Exon 1 of 7	1		ENSP00000488332.1
COMMD10	ENST00000507356.5	n.4G>C		non_coding_transcript_exon_variant	Exon 1 of 7	3		ENSP00000422448.1
ENSG00000271918	ENST00000606662.2	n.389C>G		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 16, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.4G>C (p.A2P) alteration is located in exon 1 (coding exon 1) of the COMMD10 gene. This alteration results from a G to C substitution at nucleotide position 4, causing the alanine (A) at amino acid position 2 to be replaced by a proline (P). 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	0.15
BayesDel_addAF	Benign	-0.043	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.0075	T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.47	T
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.69	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.95	N
REVEL	Benign	0.099
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.023	D
Polyphen		0.70	P
Vest4		0.62
MutPred		0.29		Gain of disorder (P = 0.0597);
MVP		0.47
MPC		0.020
ClinPred		0.81	D
GERP RS		2.8
Varity_R		0.28
gMVP		0.60

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-115420753;