rs138664639

Variant names:

• chr19-54143150-C-G
• rs138664639
• NM_014516.4:c.57C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-54143150-C-G
• chr19-54143150-C-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_014516.4(CNOT3):​c.57C>G​(p.Ser19Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,698 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S19S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CNOT3 NM_014516.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0510
• Publications: 0 publications found

Genes affected

CNOT3 (HGNC:7879): (CCR4-NOT transcription complex subunit 3) Involved in regulation of stem cell population maintenance. Part of CCR4-NOT complex. [provided by Alliance of Genome Resources, Apr 2022]

CNOT3 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• intellectual developmental disorder with speech delay, autism, and dysmorphic facies

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP7: Synonymous conserved (PhyloP=-0.051 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014516.4. 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
	CNOT3	NM_014516.4	MANE Select	c.57C>G	p.Ser19Ser	synonymous	Exon 3 of 18	NP_055331.1	O75175
	CNOT3	NM_001440653.1		c.57C>G	p.Ser19Ser	synonymous	Exon 3 of 18	NP_001427582.1
	CNOT3	NM_001440654.1		c.57C>G	p.Ser19Ser	synonymous	Exon 3 of 18	NP_001427583.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNOT3	ENST00000221232.11	TSL:1 MANE Select	c.57C>G	p.Ser19Ser	synonymous	Exon 3 of 18	ENSP00000221232.5	O75175
	CNOT3	ENST00000358389.7	TSL:1	c.57C>G	p.Ser19Ser	synonymous	Exon 2 of 17	ENSP00000351159.4	O75175
	CNOT3	ENST00000896564.1		c.57C>G	p.Ser19Ser	synonymous	Exon 3 of 18	ENSP00000566623.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461698 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727134

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53288

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111952

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	11
DANN	Benign	0.71
PhyloP100		-0.051

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

dbSNP: rs138664639; hg19: chr19-54646886;