chr2-165941108-C-T

Variant names:

• chr2-165941108-C-T
• rs937191572
• NM_024753.5:c.629G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024753.5(TTC21B):​c.629G>A​(p.Ser210Asn) 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. 17/22 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: TTC21B NM_024753.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.16
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14710104).

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.629G>A	p.Ser210Asn	missense	Exon 6 of 29	NP_079029.3
	TTC21B-AS1	NR_038983.1		n.277-6089C>T		intron	N/A
	TTC21B-AS1	NR_038984.1		n.221-6089C>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.629G>A	p.Ser210Asn	missense	Exon 6 of 29	ENSP00000243344.7	Q7Z4L5-1
	TTC21B	ENST00000464374.5	TSL:1	n.669G>A		non_coding_transcript_exon	Exon 6 of 11
	TTC21B	ENST00000679840.1		c.629G>A	p.Ser210Asn	missense	Exon 6 of 27	ENSP00000505248.1	A0A7P0T8P4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Nephronophthisis 12 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	7.9
DANN	Benign	0.80
DEOGEN2	Benign	0.056	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.51
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.42	N
PhyloP100		1.2
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.55	N
REVEL	Benign	0.10
Sift	Benign	0.49	T
Sift4G	Benign	0.37	T
Polyphen		0.0070	B
Vest4		0.084
MutPred		0.56		Loss of helix (P = 0.2271)
MVP		0.44
MPC		0.030
ClinPred		0.054	T
GERP RS		2.5
Varity_R		0.021
gMVP		0.11
Mutation Taster		=93/7	polymorphism

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: rs937191572; hg19: chr2-166797618;