8-144851323-C-T

Variant names:

• chr8-144851323-C-T
• rs1209879
• NM_014066.4:c.16G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014066.4(COMMD5):​c.16G>A​(p.Ala6Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 1,608,156 control chromosomes in the GnomAD database, including 100,539 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.28 (7162 hom., cov: 32)
  • Exomes 𝑓: 0.35 (93377 hom.)
• Consequence: COMMD5 NM_014066.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.500
• Publications: 31 publications found

Genes affected

COMMD5 (HGNC:17902): (COMM domain containing 5) Predicted to be involved in proximal tubule morphogenesis. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=6.0510635E-4).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014066.4. 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
	COMMD5	NM_014066.4	MANE Select	c.16G>A	p.Ala6Thr	missense	Exon 2 of 2	NP_054785.2
	COMMD5	NM_001081003.3		c.16G>A	p.Ala6Thr	missense	Exon 2 of 2	NP_001074472.1	Q9GZQ3
	COMMD5	NM_001081004.3		c.16G>A	p.Ala6Thr	missense	Exon 2 of 2	NP_001074473.1	Q9GZQ3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COMMD5	ENST00000305103.4	TSL:1 MANE Select	c.16G>A	p.Ala6Thr	missense	Exon 2 of 2	ENSP00000304544.3	Q9GZQ3
	COMMD5	ENST00000402718.4	TSL:1	c.16G>A	p.Ala6Thr	missense	Exon 2 of 2	ENSP00000385793.3	Q9GZQ3
	COMMD5	ENST00000450361.2	TSL:1	c.16G>A	p.Ala6Thr	missense	Exon 2 of 2	ENSP00000394331.2	Q9GZQ3

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42835 AN: 151924 Hom.: 7170 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.290

GnomAD2 exomes AF: 0.327 AC: 81563 AN: 249210 AF XY: 0.345

Gnomad AFR exome AF: 0.0942

Gnomad AMR exome AF: 0.179

Gnomad ASJ exome AF: 0.415

Gnomad EAS exome AF: 0.319

Gnomad FIN exome AF: 0.330

Gnomad NFE exome AF: 0.363

Gnomad OTH exome AF: 0.341

GnomAD4 exome AF: 0.353 AC: 513617 AN: 1456112 Hom.: 93377 Cov.: 48 AF XY: 0.358 AC XY: 259024 AN XY: 723384

African (AFR) AF: 0.0880 AC: 2935 AN: 33366

American (AMR) AF: 0.193 AC: 8574 AN: 44448

Ashkenazi Jewish (ASJ) AF: 0.406 AC: 10510 AN: 25916

East Asian (EAS) AF: 0.269 AC: 10655 AN: 39548

South Asian (SAS) AF: 0.451 AC: 38779 AN: 85972

European-Finnish (FIN) AF: 0.332 AC: 17644 AN: 53080

Middle Eastern (MID) AF: 0.273 AC: 1566 AN: 5742

European-Non Finnish (NFE) AF: 0.363 AC: 402072 AN: 1107926

Other (OTH) AF: 0.347 AC: 20882 AN: 60114

GnomAD4 genome AF: 0.282 AC: 42830 AN: 152044 Hom.: 7162 Cov.: 32 AF XY: 0.280 AC XY: 20823 AN XY: 74312

African (AFR) AF: 0.102 AC: 4250 AN: 41514

American (AMR) AF: 0.255 AC: 3897 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 1417 AN: 3468

East Asian (EAS) AF: 0.323 AC: 1663 AN: 5152

South Asian (SAS) AF: 0.453 AC: 2185 AN: 4822

European-Finnish (FIN) AF: 0.331 AC: 3495 AN: 10548

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.365 AC: 24831 AN: 67944

Other (OTH) AF: 0.290 AC: 612 AN: 2112

Alfa AF: 0.337 Hom.: 25885

Bravo AF: 0.266

TwinsUK AF: 0.371 AC: 1375

ALSPAC AF: 0.356 AC: 1373

ESP6500AA AF: 0.101 AC: 447

ESP6500EA AF: 0.363 AC: 3126

ExAC AF: 0.328 AC: 39845

Asia WGS AF: 0.421 AC: 1465 AN: 3478

EpiCase AF: 0.372

EpiControl AF: 0.368

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	4.6
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0031	T
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.074	N
LIST_S2	Benign	0.54	T
MetaRNN	Benign	0.00061	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.50
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.33	N
REVEL	Benign	0.062
Sift	Benign	0.35	T
Sift4G	Benign	0.12	T
Polyphen		0.099	B
Vest4		0.026
MPC		0.13
ClinPred		0.00070	T
GERP RS		1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
Varity_R		0.016
gMVP		0.30
Mutation Taster		=97/3	polymorphism (auto)

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: rs1209879; hg19: chr8-146076708; COSMIC: COSV59310992; COSMIC: COSV59310992;