NM_024753.5:c.710+87G>A

Variant names:

• chr2-165940940-C-T
• rs7592392
• NM_024753.5:c.710+87G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024753.5(TTC21B):​c.710+87G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000152 in 1,313,002 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: TTC21B NM_024753.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.952
• Publications: 2 publications found

Genes affected

TTC21B (HGNC:25660): (tetratricopeptide repeat domain 21B) This gene encodes a member of TTC21 family, containing several tetratricopeptide repeat (TPR) domains. This protein is localized to the cilium axoneme, and may play a role in retrograde intraflagellar transport in cilia. Mutations in this gene are associated with various ciliopathies, nephronophthisis 12, and asphyxiating thoracic dystrophy 4. [provided by RefSeq, Oct 2011]

TTC21B-AS1 (HGNC:41115): (TTC21B antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024753.5. 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
	TTC21B	NM_024753.5	MANE Select	c.710+87G>A		intron	N/A	NP_079029.3
	TTC21B-AS1	NR_038983.1		n.276+6151C>T		intron	N/A
	TTC21B-AS1	NR_038984.1		n.221-6257C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC21B	ENST00000243344.8	TSL:1 MANE Select	c.710+87G>A		intron	N/A	ENSP00000243344.7	Q7Z4L5-1
	TTC21B	ENST00000464374.5	TSL:1	n.750+87G>A		intron	N/A
	TTC21B	ENST00000679840.1		c.710+87G>A		intron	N/A	ENSP00000505248.1	A0A7P0T8P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000152 AC: 2 AN: 1313002 Hom.: 0 AF XY: 0.00000152 AC XY: 1 AN XY: 659710

African (AFR) AF: 0.0000334 AC: 1 AN: 29984

American (AMR) AF: 0.00 AC: 0 AN: 42144

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24980

East Asian (EAS) AF: 0.00 AC: 0 AN: 38660

South Asian (SAS) AF: 0.0000124 AC: 1 AN: 80910

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52126

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4286

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 984756

Other (OTH) AF: 0.00 AC: 0 AN: 55156

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 2231

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.15
DANN	Benign	0.73
PhyloP100		-0.95

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: rs7592392; hg19: chr2-166797450;