rs10055

Variant names:

• chr16-24824555-T-C
• rs10055
• NM_014494.4:c.*748T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014494.4(TNRC6A):​c.*748T>C variant causes a 3 prime UTR change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 30)
• Consequence: TNRC6A NM_014494.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.84
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• epilepsy, familial adult myoclonic, 6

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014494.4. 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
	TNRC6A	NM_014494.4	MANE Select	c.*748T>C		3_prime_UTR	Exon 25 of 25	NP_055309.2	Q8NDV7-1
	TNRC6A	NM_001351850.2		c.*748T>C		3_prime_UTR	Exon 24 of 24	NP_001338779.1
	TNRC6A	NM_001330520.3		c.*748T>C		3_prime_UTR	Exon 24 of 24	NP_001317449.1	Q8NDV7-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNRC6A	ENST00000395799.8	TSL:5 MANE Select	c.*748T>C		3_prime_UTR	Exon 25 of 25	ENSP00000379144.3	Q8NDV7-1
	TNRC6A	ENST00000464539.1	TSL:1	n.1622T>C		non_coding_transcript_exon	Exon 3 of 3
	TNRC6A	ENST00000491718.5	TSL:1	n.*6162T>C		non_coding_transcript_exon	Exon 22 of 22	ENSP00000460688.1	I3L3S5

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	17
DANN	Benign	0.91
PhyloP100		7.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10055;

hg19: chr16-24835876;