3-28241803-G-A

Position:

• chr3-28241803-G-A

Variant summary

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

The NM_182523.2(CMC1):​c.10G>A​(p.Asp4Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/19 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CMC1 NM_182523.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.61

Genes affected

CMC1 (HGNC:28783): (C-X9-C motif containing 1) Predicted to enable metal ion binding activity. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

CMC1 (HGNC:):

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=0.22746342).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CMC1	NM_182523.2	c.10G>A	p.Asp4Asn	missense_variant	1/4	ENST00000466830.6	NP_872329.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CMC1	ENST00000466830.6	c.10G>A	p.Asp4Asn	missense_variant	1/4	1	NM_182523.2	ENSP00000418348.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1087678 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 513742

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 01, 2024

The c.10G>A (p.D4N) alteration is located in exon 1 (coding exon 1) of the CMC1 gene. This alteration results from a G to A substitution at nucleotide position 10, causing the aspartic acid (D) at amino acid position 4 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.44	T;T
Eigen	Benign	-0.091
Eigen_PC	Benign	0.039
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.57	T;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-0.90	T
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-3.3	D;N
REVEL	Benign	0.14
Sift	Benign	0.15	T;D
Sift4G	Benign	0.20	T;D
Polyphen		0.26	B;.
Vest4		0.31
MutPred		0.56		Loss of disorder (P = 0.0898);Loss of disorder (P = 0.0898);
MVP		0.11
MPC		0.016
ClinPred		0.92	D
GERP RS		4.2
Varity_R		0.27
gMVP		0.20

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: chr3-28283294;