8-144851323-C-T

Position:

• chr8-144851323-C-T

Variant summary

Our verdict is Benign. Variant got -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. 12/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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]

COMMD5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COMMD5	NM_014066.4	c.16G>A	p.Ala6Thr	missense_variant	2/2	ENST00000305103.4	NP_054785.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COMMD5	ENST00000305103.4	c.16G>A	p.Ala6Thr	missense_variant	2/2	1	NM_014066.4	ENSP00000304544.3

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

GnomAD3 exomes AF: 0.327 AC: 81563 AN: 249210 Hom.: 14698 AF XY: 0.345 AC XY: 46501 AN XY: 134710

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 SAS exome AF: 0.457

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

Gnomad4 AFR exome AF: 0.0880

Gnomad4 AMR exome AF: 0.193

Gnomad4 ASJ exome AF: 0.406

Gnomad4 EAS exome AF: 0.269

Gnomad4 SAS exome AF: 0.451

Gnomad4 FIN exome AF: 0.332

Gnomad4 NFE exome AF: 0.363

Gnomad4 OTH exome AF: 0.347

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

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.255

Gnomad4 ASJ AF: 0.409

Gnomad4 EAS AF: 0.323

Gnomad4 SAS AF: 0.453

Gnomad4 FIN AF: 0.331

Gnomad4 NFE AF: 0.365

Gnomad4 OTH AF: 0.290

Alfa AF: 0.352 Hom.: 20585

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 v4.3

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;T;T;T;.;.
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.074	N
LIST_S2	Benign	0.54	.;T;.;.;.;T
MetaRNN	Benign	0.00061	T;T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.1	L;L;L;L;.;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.33	N;.;N;N;N;N
REVEL	Benign	0.062
Sift	Benign	0.35	T;.;T;T;T;T
Sift4G	Benign	0.12	T;T;T;T;.;T
Polyphen		0.099	B;B;B;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

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

LitVar

Other links and lift over

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