Genetic Variant COMMD9:p.Ala79Ala (chr11-36278557-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2

The NM_014186.4(COMMD9):c.237C>T(p.Ala79Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00299 in 1,614,072 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0031 ( 8 hom. )

Consequence

COMMD9
NM_014186.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.71

Variant links:

Genes affected

COMMD9 (HGNC:25014): (COMM domain containing 9) Predicted to be involved in sodium ion transport. Predicted to act upstream of or within cholesterol homeostasis. Located in Golgi apparatus; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

COMMD9 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP6

Variant 11-36278557-G-A is Benign according to our data. Variant chr11-36278557-G-A is described in ClinVar as [Benign]. Clinvar id is 708568.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COMMD9	NM_014186.4 link	c.237C>T	p.Ala79Ala	synonymous_variant	Exon 3 of 6	ENST00000263401.10	NP_054905.2	Q9P000-1Q53FR9
COMMD9	NM_001307937.2 link	c.210C>T	p.Ala70Ala	synonymous_variant	Exon 4 of 7		NP_001294866.1	Q9P000Q53FR9
COMMD9	NM_001307932.2 link	c.237C>T	p.Ala79Ala	synonymous_variant	Exon 3 of 5		NP_001294861.1	Q53FR9E9PJ95
COMMD9	NM_001101653.2 link	c.111C>T	p.Ala37Ala	synonymous_variant	Exon 2 of 5		NP_001095123.1	Q53FR9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COMMD9	ENST00000263401.10 link	c.237C>T	p.Ala79Ala	synonymous_variant	Exon 3 of 6	1	NM_014186.4	ENSP00000263401.5		Q9P000-1

Frequencies

GnomAD3 genomes

AF:

0.00206

AC:

314

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000962

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00372

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00211

AC:

531

AN:

251338

Hom.:

AF XY:

0.00215

AC XY:

292

AN XY:

135838

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.000607

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00109

Gnomad SAS exome

AF:

0.000882

Gnomad FIN exome

AF:

0.000971

Gnomad NFE exome

AF:

0.00374

Gnomad OTH exome

AF:

0.00130

GnomAD4 exome

AF:

0.00309

AC:

4511

AN:

1461758

Hom.:

Cov.:

AF XY:

0.00298

AC XY:

2167

AN XY:

727180

show subpopulations

Gnomad4 AFR exome

AF:

0.000627

Gnomad4 AMR exome

AF:

0.000581

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.000504

Gnomad4 SAS exome

AF:

0.00104

Gnomad4 FIN exome

AF:

0.00109

Gnomad4 NFE exome

AF:

0.00370

Gnomad4 OTH exome

AF:

0.00272

GnomAD4 genome

AF:

0.00206

AC:

314

AN:

152314

Hom.:

Cov.:

AF XY:

0.00200

AC XY:

149

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.000505

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000965

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.00372

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00315

Hom.:

Bravo

AF:

0.00200

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00398

EpiControl

AF:

0.00279

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 20, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.26

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.26

Position offset: -26

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over