rs759898407

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_016144.4(COMMD10):​c.10C>A​(p.Pro4Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,084 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. P4S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

COMMD10
NM_016144.4 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.19
Variant links:
Genes affected
COMMD10 (HGNC:30201): (COMM domain containing 10) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.041858256).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
COMMD10NM_016144.4 linkc.10C>A p.Pro4Thr missense_variant Exon 1 of 7 ENST00000274458.9 NP_057228.1 Q9Y6G5
COMMD10NR_146218.2 linkn.38C>A non_coding_transcript_exon_variant Exon 1 of 7
COMMD10NR_146220.2 linkn.38C>A non_coding_transcript_exon_variant Exon 1 of 8
COMMD10NR_146219.2 linkn.-216C>A upstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
COMMD10ENST00000274458.9 linkc.10C>A p.Pro4Thr missense_variant Exon 1 of 7 1 NM_016144.4 ENSP00000274458.4 Q9Y6G5
COMMD10ENST00000632434 linkc.-33C>A 5_prime_UTR_variant Exon 1 of 7 1 ENSP00000488332.1 D6RJ90
COMMD10ENST00000507356.5 linkn.10C>A non_coding_transcript_exon_variant Exon 1 of 7 3 ENSP00000422448.1 D6RC04
ENSG00000271918ENST00000606662.2 linkn.383G>T non_coding_transcript_exon_variant Exon 1 of 1 6

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.86e-7
AC:
1
AN:
1457084
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
724556
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.065
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.70
CADD
Benign
0.74
DANN
Benign
0.74
DEOGEN2
Benign
0.0022
T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.031
N
LIST_S2
Benign
0.62
T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.042
T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
0.69
N
PrimateAI
Uncertain
0.52
T
PROVEAN
Benign
0.62
N
REVEL
Benign
0.032
Sift
Benign
0.30
T
Sift4G
Benign
0.21
T
Polyphen
0.0
B
Vest4
0.13
MutPred
0.15
Gain of helix (P = 0.0425);
MVP
0.072
MPC
0.0056
ClinPred
0.059
T
GERP RS
-1.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.7
Varity_R
0.034
gMVP
0.44

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: chr5-115420759; API