rs1209879

Positions:

• chr8-144851323-C-A
• chr8-144851323-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014066.4(COMMD5):​c.16G>T​(p.Ala6Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. A6T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• 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]

ACMG classification

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=0.043089688).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COMMD5	NM_014066.4	c.16G>T	p.Ala6Ser	missense_variant	2/2	ENST00000305103.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COMMD5	ENST00000305103.4	c.16G>T	p.Ala6Ser	missense_variant	2/2	1	NM_014066.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 48

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	2.2
DANN	Benign	0.87
DEOGEN2	Benign	0.0011	T;T;T;T;.;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.084	N
LIST_S2	Benign	0.53	.;T;.;.;.;T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.043	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;N;N;N;.;.
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.15	N;.;N;N;N;N
REVEL	Benign	0.020
Sift	Benign	0.44	T;.;T;T;T;T
Sift4G	Benign	0.50	T;T;T;T;.;T
Polyphen		0.0030	B;B;B;B;.;.
Vest4		0.070
MutPred		0.17		Gain of glycosylation at A6 (P = 0.0053);Gain of glycosylation at A6 (P = 0.0053);Gain of glycosylation at A6 (P = 0.0053);Gain of glycosylation at A6 (P = 0.0053);Gain of glycosylation at A6 (P = 0.0053);Gain of glycosylation at A6 (P = 0.0053);
MVP		0.23
MPC		0.13
ClinPred		0.025	T
GERP RS		1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
Varity_R		0.018
gMVP		0.25

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;