16-24776996-C-T

Position:

• chr16-24776996-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014494.4(TNRC6A):​c.227C>T​(p.Ser76Phe) variant causes a missense change. 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: 32)
• Consequence: TNRC6A NM_014494.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.99

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20679799).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNRC6A	NM_014494.4	c.227C>T	p.Ser76Phe	missense_variant	5/25	ENST00000395799.8	NP_055309.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNRC6A	ENST00000395799.8	c.227C>T	p.Ser76Phe	missense_variant	5/25	5	NM_014494.4	ENSP00000379144.3
TNRC6A	ENST00000315183.11	c.227C>T	p.Ser76Phe	missense_variant	5/24	5		ENSP00000326900.7
TNRC6A	ENST00000562829.1	n.246C>T		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 21, 2024

The c.227C>T (p.S76F) alteration is located in exon 5 (coding exon 5) of the TNRC6A gene. This alteration results from a C to T substitution at nucleotide position 227, causing the serine (S) at amino acid position 76 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.035	.;T
Eigen	Uncertain	0.19
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.97	L;L
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.058
Sift	Uncertain	0.0010	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.39	.;B
Vest4		0.48
MutPred		0.28		Loss of glycosylation at S76 (P = 0.0034);Loss of glycosylation at S76 (P = 0.0034);
MVP		0.19
MPC		0.48
ClinPred		0.78	D
GERP RS		5.0
Varity_R		0.35
gMVP		0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: chr16-24788317; COSMIC: COSV105125695; COSMIC: COSV105125695;