3-32720118-C-T

Variant names:

• chr3-32720118-C-T
• NM_015442.3:c.749C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015442.3(CNOT10):​c.749C>T​(p.Ala250Val) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CNOT10 NM_015442.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.15
• Publications: 0 publications found

Genes affected

CNOT10 (HGNC:23817): (CCR4-NOT transcription complex subunit 10) Predicted to be involved in mRNA catabolic process and negative regulation of translation. Located in membrane. Part of CCR4-NOT complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2927611).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015442.3. 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
	CNOT10	NM_015442.3	MANE Select	c.749C>T	p.Ala250Val	missense	Exon 8 of 19	NP_056257.1	Q9H9A5-1
	CNOT10	NM_001256742.2		c.929C>T	p.Ala310Val	missense	Exon 8 of 19	NP_001243671.1	Q9H9A5-6
	CNOT10	NM_001393366.1		c.749C>T	p.Ala250Val	missense	Exon 8 of 19	NP_001380295.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNOT10	ENST00000328834.10	TSL:1 MANE Select	c.749C>T	p.Ala250Val	missense	Exon 8 of 19	ENSP00000330060.5	Q9H9A5-1
	CNOT10	ENST00000331889.10	TSL:1	c.749C>T	p.Ala250Val	missense	Exon 8 of 18	ENSP00000329376.6	Q9H9A5-3
	CNOT10	ENST00000435630.5	TSL:1	n.587C>T		non_coding_transcript_exon	Exon 7 of 17	ENSP00000402795.1	E9PCN5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1346934 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 666572

African (AFR) AF: 0.00 AC: 0 AN: 31954

American (AMR) AF: 0.00 AC: 0 AN: 43632

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23766

East Asian (EAS) AF: 0.00 AC: 0 AN: 38824

South Asian (SAS) AF: 0.00 AC: 0 AN: 71986

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49664

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5310

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1026940

Other (OTH) AF: 0.00 AC: 0 AN: 54858

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.028
Eigen_PC	Benign	0.21
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	1.0	L
PhyloP100		6.1
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.53	N
REVEL	Benign	0.18
Sift	Benign	0.24	T
Sift4G	Benign	0.46	T
Polyphen		0.0070	B
Vest4		0.61
MutPred		0.25		Loss of helix (P = 0.0626)
MVP		0.52
MPC		0.46
ClinPred		0.80	D
GERP RS		5.9
Varity_R		0.14
gMVP		0.62
Mutation Taster		=24/76	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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

hg19: chr3-32761610;