rs1055081896

Variant names:

• chr17-7577851-C-T
• rs1055081896
• NM_001416.4:c.931C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-7577851-C-T
• chr17-7577851-C-A

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_001416.4(EIF4A1):​c.931C>T​(p.Arg311*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 31)
• Consequence: EIF4A1 NM_001416.4 stop_gained
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.430
• Publications: 0 publications found

Genes affected

EIF4A1 (HGNC:3282): (eukaryotic translation initiation factor 4A1) Enables double-stranded RNA binding activity. Predicted to be involved in cytoplasmic translational initiation. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

SENP3-EIF4A1 (HGNC:49182): (SENP3-EIF4A1 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring SUMO1/sentrin/SMT3 specific peptidase 3 (SENP3) and eukaryotic translation initiation factor 4A1 (EIF4A1) genes on chromosome 17. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Mar 2011]

ENSG00000264772 (HGNC:):

SNORA67 (HGNC:10224): (small nucleolar RNA, H/ACA box 67)

ACMG classification

Our verdict: Pathogenic. The variant received 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001416.4. 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
	EIF4A1	NM_001416.4	MANE Select	c.931C>T	p.Arg311*	stop_gained	Exon 9 of 11	NP_001407.1	P60842-1
	EIF4A1	NM_001204510.2		c.931C>T	p.Arg311*	stop_gained	Exon 9 of 11	NP_001191439.1	P60842-2
	SENP3-EIF4A1	NR_037926.1		n.3493C>T		non_coding_transcript_exon	Exon 20 of 22

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF4A1	ENST00000293831.13	TSL:1 MANE Select	c.931C>T	p.Arg311*	stop_gained	Exon 9 of 11	ENSP00000293831.8	P60842-1
	EIF4A1	ENST00000577269.5	TSL:1	c.931C>T	p.Arg311*	stop_gained	Exon 9 of 11	ENSP00000463486.1	P60842-2
	SENP3-EIF4A1	ENST00000614237.1	TSL:2	n.*1377C>T		non_coding_transcript_exon	Exon 19 of 21	ENSP00000483614.1	A0A087X0R7

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Autism spectrum disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.53	D
BayesDel_noAF	Pathogenic	0.52
CADD	Pathogenic	37
DANN	Uncertain	1.0
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.79	D
PhyloP100		0.43
Vest4		0.90
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1055081896; hg19: chr17-7481169;