Variant chr3-39112464-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001366900.1(TTC21A):c.442G>A(p.Val148Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,170 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

TTC21A
NM_001366900.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.86

Variant links:

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]

TTC21A links:

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ACMG classification

Classification made for transcript

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=0.20380095).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC21A	NM_001366900.1 linkuse as main transcript	c.442G>A	p.Val148Met	missense_variant	5/29	ENST00000683103.1	NP_001353829.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC21A	ENST00000683103.1 linkuse as main transcript	c.442G>A	p.Val148Met	missense_variant	5/29		NM_001366900.1	ENSP00000507739	P1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152170

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 30, 2024

The c.442G>A (p.V148M) alteration is located in exon 5 (coding exon 5) of the TTC21A gene. This alteration results from a G to A substitution at nucleotide position 442, causing the valine (V) at amino acid position 148 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

0.21

BayesDel_addAF

Uncertain

0.058

BayesDel_noAF

Benign

-0.15

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.016

Eigen

Benign

0.080

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.79

M_CAP

Benign

0.034

MetaRNN

Benign

0.20

MetaSVM

Benign

-0.63

MutationAssessor

Uncertain

2.3

MutationTaster

Benign

0.91

D;D;D

PrimateAI

Benign

0.46

PROVEAN

Benign

-2.0

REVEL

Benign

0.14

Sift

Uncertain

0.012

Sift4G

Uncertain

0.033

Polyphen

0.13

Vest4

0.25

MutPred

0.41

Gain of MoRF binding (P = 0.0806);

MVP

0.76

MPC

0.20

ClinPred

0.91

GERP RS

5.7

Varity_R

0.092

gMVP

0.19

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over