3-39110894-A-G

Variant names:

• chr3-39110894-A-G
• NM_001366900.1:c.312A>G

Variant summary

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

The NM_001366900.1(TTC21A):​c.312A>G​(p.Ile104Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TTC21A NM_001366900.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.281

Genes affected

TTC21A (HGNC:30761): (tetratricopeptide repeat domain 21A) Involved in flagellated sperm motility and spermatid development. Predicted to be located in cilium. Predicted to be part of intraciliary transport particle A. Implicated in spermatogenic failure 37. [provided by Alliance of Genome Resources, Apr 2022]

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=0.12278825).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC21A	NM_001366900.1	c.312A>G	p.Ile104Met	missense_variant	Exon 4 of 29	ENST00000683103.1	NP_001353829.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC21A	ENST00000683103.1	c.312A>G	p.Ile104Met	missense_variant	Exon 4 of 29		NM_001366900.1	ENSP00000507739.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.312A>G (p.I104M) alteration is located in exon 4 (coding exon 4) of the TTC21A gene. This alteration results from a A to G substitution at nucleotide position 312, causing the isoleucine (I) at amino acid position 104 to be replaced by a methionine (M). 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	0.057
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	3.3
DANN	Benign	0.97
DEOGEN2	Benign	0.0044	T;.
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.48	T;T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.1	M;M
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.23	N;N
REVEL	Benign	0.075
Sift	Benign	0.12	T;T
Sift4G	Benign	0.11	T;T
Polyphen		0.61	P;P
Vest4		0.21
MutPred		0.33		Gain of glycosylation at T107 (P = 0.0157);Gain of glycosylation at T107 (P = 0.0157);
MVP		0.61
MPC		0.23
ClinPred		0.13	T
GERP RS		0.23
Varity_R		0.059
gMVP		0.075

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-39152385;