Genetic Variant COMMD10:p.Pro4Ser (chr5-116085062-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_016144.4(COMMD10):c.10C>T(p.Pro4Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000621 in 1,609,332 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

COMMD10
NM_016144.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.19

Publications

1 publications found

Variant links:

Genes affected

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

COMMD10 links:

ENSG00000271918 (HGNC:58400):

ENSG00000271918 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.019364268).

BP6

Variant 5-116085062-C-T is Benign according to our data. Variant chr5-116085062-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2347479.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016144.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COMMD10	NM_016144.4	MANE Select	c.10C>T	p.Pro4Ser	missense	Exon 1 of 7	NP_057228.1	Q9Y6G5
COMMD10	NR_146218.2		n.38C>T		non_coding_transcript_exon	Exon 1 of 7
COMMD10	NR_146220.2		n.38C>T		non_coding_transcript_exon	Exon 1 of 8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COMMD10	ENST00000274458.9	TSL:1 MANE Select	c.10C>T	p.Pro4Ser	missense	Exon 1 of 7	ENSP00000274458.4	Q9Y6G5
COMMD10	ENST00000632434.1	TSL:1	c.-33C>T		5_prime_UTR	Exon 1 of 7	ENSP00000488332.1	D6RJ90
COMMD10	ENST00000908482.1		c.10C>T	p.Pro4Ser	missense	Exon 1 of 5	ENSP00000578541.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000340

AC:

AN:

235326

AF XY:

0.0000388

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000568

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000960

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000618

AC:

AN:

1457084

Hom.:

Cov.:

AF XY:

0.00000828

AC XY:

AN XY:

724556

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33376

American (AMR)

AF:

0.00

AC:

AN:

44446

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25964

East Asian (EAS)

AF:

0.00

AC:

AN:

39500

South Asian (SAS)

AF:

0.0000703

AC:

AN:

85358

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51900

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5532

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1110864

Other (OTH)

AF:

0.0000333

AC:

AN:

60144

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.403

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152248

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41470

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68042

Other (OTH)

AF:

0.000478

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000413

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.72

CADD

Benign

1.1

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.0022

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0057

LIST_S2

Benign

0.62

M_CAP

Benign

0.016

MetaRNN

Benign

0.019

MetaSVM

Benign

-0.86

MutationAssessor

Benign

-0.41

PhyloP100

-1.2

PrimateAI

Uncertain

0.51

PROVEAN

Benign

1.1

REVEL

Benign

0.029

Sift

Benign

1.0

Sift4G

Benign

0.61

Polyphen

0.0

Vest4

0.080

MutPred

0.21

Loss of loop (P = 0.0073)

MVP

0.048

MPC

0.0058

ClinPred

0.028

GERP RS

-1.5

PromoterAI

0.15

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.021

gMVP

0.38

Mutation Taster

=93/7

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over