chr16-24750807-AAAG-A

Position:

• chr16-24750807-AAAG-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PM4_Supporting

The NM_014494.4(TNRC6A):​c.139_141delAAG​(p.Lys47del) variant causes a conservative inframe deletion, splice region change. The variant was absent in control chromosomes in GnomAD project. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TNRC6A NM_014494.4 conservative_inframe_deletion, splice_region
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.72

Genes affected

TNRC6A (HGNC:11969): (trinucleotide repeat containing adaptor 6A) This gene encodes a member of the trinucleotide repeat containing 6 protein family. The protein functions in post-transcriptional gene silencing through the RNA interference (RNAi) and microRNA pathways. The protein associates with messenger RNAs and Argonaute proteins in cytoplasmic bodies known as GW-bodies or P-bodies. Inhibiting expression of this gene delocalizes other GW-body proteins and impairs RNAi and microRNA-induced gene silencing. [provided by RefSeq, Jul 2008]

TNRC6A (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_014494.4. Strenght limited to Supporting due to length of the change: 1aa.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNRC6A	NM_014494.4	c.139_141delAAG	p.Lys47del	conservative_inframe_deletion, splice_region_variant	3/25	ENST00000395799.8	NP_055309.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNRC6A	ENST00000395799.8	c.139_141delAAG	p.Lys47del	conservative_inframe_deletion, splice_region_variant	3/25	5	NM_014494.4	ENSP00000379144.3
TNRC6A	ENST00000315183.11	c.139_141delAAG	p.Lys47del	conservative_inframe_deletion, splice_region_variant	3/24	5		ENSP00000326900.7
TNRC6A	ENST00000562829.1	n.182+20511_182+20513delAAG		intron_variant		2
TNRC6A	ENST00000566108.2	n.*31_*33delAAG		downstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Epilepsy, familial adult myoclonic, 6 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

New York Genome Center

Oct 08, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: chr16-24762128;