rs757171818

Variant names:

• chr19-54155813-C-A
• rs757171818
• NM_024316.3:c.703G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-54155813-C-A
• chr19-54155813-C-G
• chr19-54155813-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_024316.3(LENG1):​c.703G>T​(p.Glu235*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,460,136 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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: 0.0000041 (0 hom.)
• Consequence: LENG1 NM_024316.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.84
• Publications: 0 publications found

Genes affected

LENG1 (HGNC:15502): (leukocyte receptor cluster member 1)

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: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LENG1	NM_024316.3	c.703G>T	p.Glu235*	stop_gained	Exon 4 of 4	ENST00000222224.4	NP_077292.2
CNOT3	NM_014516.4	c.*406C>A		downstream_gene_variant		ENST00000221232.11	NP_055331.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LENG1	ENST00000222224.4	c.703G>T	p.Glu235*	stop_gained	Exon 4 of 4	1	NM_024316.3	ENSP00000222224.3
CNOT3	ENST00000221232.11	c.*406C>A		downstream_gene_variant		1	NM_014516.4	ENSP00000221232.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000163 AC: 4 AN: 245216 AF XY: 0.0000150

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000117

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1460136 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 726300

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.000112 AC: 5 AN: 44630

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25978

East Asian (EAS) AF: 0.00 AC: 0 AN: 39670

South Asian (SAS) AF: 0.00 AC: 0 AN: 85966

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111792

Other (OTH) AF: 0.00 AC: 0 AN: 60300

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.47
CADD	Pathogenic	35
DANN	Uncertain	0.99
Eigen	Uncertain	0.29
Eigen_PC	Benign	-0.044
FATHMM_MKL	Uncertain	0.86	D
PhyloP100		1.8
Vest4		0.12
GERP RS		3.1
Mutation Taster		=27/173	disease causing

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

Other links and lift over

dbSNP: rs757171818; hg19: chr19-54659551;