10-22318964-T-G

Variant names:

• chr10-22318964-T-G
• ENST00000602390.5:c.356T>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001204062.2(COMMD3-BMI1):​c.356T>G​(p.Leu119Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/16 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: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: COMMD3-BMI1 NM_001204062.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.391

Genes affected

COMMD3-BMI1 (HGNC:48326): (COMMD3-BMI1 readthrough) This locus represents naturally occurring read-through transcription between the neighboring COMM domain-containing protein 3 and polycomb complex protein BMI-1 genes on chromosome 10. The read-through transcript produces a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Feb 2011]

COMMD3 (HGNC:23332): (COMM domain containing 3) Predicted to be involved in sodium ion transport. Predicted to be located in extracellular region and ficolin-1-rich granule lumen. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.074328005).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COMMD3	NM_012071.4	c.474T>G	p.Thr158Thr	synonymous_variant	Exon 7 of 8	ENST00000376836.8	NP_036203.1
COMMD3-BMI1	NM_001204062.2	c.356T>G	p.Leu119Arg	missense_variant	Exon 5 of 14		NP_001190991.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COMMD3-BMI1	ENST00000602390.5	c.356T>G	p.Leu119Arg	missense_variant	Exon 5 of 14	2		ENSP00000473391.1
COMMD3	ENST00000376836.8	c.474T>G	p.Thr158Thr	synonymous_variant	Exon 7 of 8	1	NM_012071.4	ENSP00000366032.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460866 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726750

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	3.4
DANN	Benign	0.80
Eigen	Benign	-0.88
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.29	T
Sift4G	Benign	0.36	T
Vest4		0.21
MVP		0.29
MPC		0.70
ClinPred		0.030	T
GERP RS		-2.2
gMVP		0.18

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-22607893;