chr3-39126792-T-C

Variant names:

• chr3-39126792-T-C
• rs811971
• NM_001366900.1:c.1522+402T>C

Variant summary

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

The NM_001366900.1(TTC21A):​c.1522+402T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.624 in 152,068 control chromosomes in the GnomAD database, including 31,936 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 0.62 (31936 hom., cov: 32)
• Consequence: TTC21A NM_001366900.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550
• Publications: 12 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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366900.1. 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
	TTC21A	NM_001366900.1	MANE Select	c.1522+402T>C		intron	N/A	NP_001353829.1	A0A804HK20
	TTC21A	NM_001366899.1		c.1546+402T>C		intron	N/A	NP_001353828.1	A0A140VJY5
	TTC21A	NM_145755.3		c.1546+402T>C		intron	N/A	NP_665698.2	Q8NDW8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC21A	ENST00000683103.1	MANE Select	c.1522+402T>C		intron	N/A	ENSP00000507739.1	A0A804HK20
	TTC21A	ENST00000431162.6	TSL:1	c.1546+402T>C		intron	N/A	ENSP00000398211.2	Q8NDW8-1
	TTC21A	ENST00000916782.1		c.1522+402T>C		intron	N/A	ENSP00000586841.1

Frequencies

GnomAD3 genomes AF: 0.624 AC: 94818 AN: 151950 Hom.: 31939 Cov.: 32

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.731

Gnomad AMR AF: 0.698

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.763

Gnomad FIN AF: 0.761

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.737

Gnomad OTH AF: 0.650

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

GnomAD4 genome AF: 0.624 AC: 94846 AN: 152068 Hom.: 31936 Cov.: 32 AF XY: 0.630 AC XY: 46821 AN XY: 74306

African (AFR) AF: 0.353 AC: 14613 AN: 41446

American (AMR) AF: 0.699 AC: 10681 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.683 AC: 2370 AN: 3472

East Asian (EAS) AF: 0.597 AC: 3080 AN: 5160

South Asian (SAS) AF: 0.763 AC: 3677 AN: 4820

European-Finnish (FIN) AF: 0.761 AC: 8042 AN: 10566

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.737 AC: 50148 AN: 67998

Other (OTH) AF: 0.648 AC: 1369 AN: 2112

Alfa AF: 0.698 Hom.: 49272

Bravo AF: 0.600

Asia WGS AF: 0.646 AC: 2251 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.4
DANN	Benign	0.82
PhyloP100		0.055
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: rs811971; hg19: chr3-39168283;