3-39132039-A-G

Variant names:

• chr3-39132039-A-G
• rs784490
• NM_001366900.1:c.2562+944A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001366900.1(TTC21A):​c.2562+944A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.684 in 151,868 control chromosomes in the GnomAD database, including 36,640 homozygotes. 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: 𝑓 0.68 (36640 hom., cov: 31)
• Consequence: TTC21A NM_001366900.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.261
• Publications: 10 publications found

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 Gene-Disease associations (from GenCC):

• spermatogenic failure 37

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• non-syndromic male infertility due to sperm motility disorder

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC21A	NM_001366900.1	c.2562+944A>G		intron_variant	Intron 19 of 28	ENST00000683103.1	NP_001353829.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC21A	ENST00000683103.1	c.2562+944A>G		intron_variant	Intron 19 of 28		NM_001366900.1	ENSP00000507739.1

Frequencies

GnomAD3 genomes AF: 0.684 AC: 103751 AN: 151750 Hom.: 36637 Cov.: 31

Gnomad AFR AF: 0.493

Gnomad AMI AF: 0.819

Gnomad AMR AF: 0.736

Gnomad ASJ AF: 0.699

Gnomad EAS AF: 0.754

Gnomad SAS AF: 0.803

Gnomad FIN AF: 0.786

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.755

Gnomad OTH AF: 0.693

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

GnomAD4 genome AF: 0.684 AC: 103803 AN: 151868 Hom.: 36640 Cov.: 31 AF XY: 0.689 AC XY: 51119 AN XY: 74246

African (AFR) AF: 0.492 AC: 20356 AN: 41334

American (AMR) AF: 0.736 AC: 11240 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.699 AC: 2423 AN: 3466

East Asian (EAS) AF: 0.754 AC: 3901 AN: 5176

South Asian (SAS) AF: 0.802 AC: 3849 AN: 4802

European-Finnish (FIN) AF: 0.786 AC: 8286 AN: 10548

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.755 AC: 51337 AN: 67962

Other (OTH) AF: 0.693 AC: 1464 AN: 2114

Alfa AF: 0.705 Hom.: 14399

Bravo AF: 0.667

Asia WGS AF: 0.734 AC: 2556 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.1
DANN	Benign	0.66
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs784490; hg19: chr3-39173530;