rs1432273

Variant names:

• chr2-165941136-C-T
• rs1432273
• NM_024753.5:c.601G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024753.5(TTC21B):​c.601G>A​(p.Val201Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.624 in 1,613,424 control chromosomes in the GnomAD database, including 316,920 homozygotes. 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 Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.62 (29894 hom., cov: 32)
  • Exomes 𝑓: 0.62 (287026 hom.)
• Consequence: TTC21B NM_024753.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 0.742
• Publications: 41 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.2303832E-6).
• BP6: Variant 2-165941136-C-T is Benign according to our data. Variant chr2-165941136-C-T is described in ClinVar as Benign. ClinVar VariationId is 130657.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

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.601G>A	p.Val201Met	missense	Exon 6 of 29	NP_079029.3
	TTC21B-AS1	NR_038983.1		n.277-6061C>T		intron	N/A
	TTC21B-AS1	NR_038984.1		n.221-6061C>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.601G>A	p.Val201Met	missense	Exon 6 of 29	ENSP00000243344.7	Q7Z4L5-1
	TTC21B	ENST00000464374.5	TSL:1	n.641G>A		non_coding_transcript_exon	Exon 6 of 11
	TTC21B	ENST00000679840.1		c.601G>A	p.Val201Met	missense	Exon 6 of 27	ENSP00000505248.1	A0A7P0T8P4

Frequencies

GnomAD3 genomes AF: 0.624 AC: 94748 AN: 151902 Hom.: 29867 Cov.: 32

Gnomad AFR AF: 0.574

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.713

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.806

Gnomad SAS AF: 0.673

Gnomad FIN AF: 0.666

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.636

GnomAD2 exomes AF: 0.664 AC: 166664 AN: 250996 AF XY: 0.660

Gnomad AFR exome AF: 0.577

Gnomad AMR exome AF: 0.783

Gnomad ASJ exome AF: 0.593

Gnomad EAS exome AF: 0.804

Gnomad FIN exome AF: 0.674

Gnomad NFE exome AF: 0.622

Gnomad OTH exome AF: 0.659

GnomAD4 exome AF: 0.624 AC: 912423 AN: 1461404 Hom.: 287026 Cov.: 50 AF XY: 0.626 AC XY: 455210 AN XY: 727010

African (AFR) AF: 0.579 AC: 19362 AN: 33462

American (AMR) AF: 0.773 AC: 34544 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.590 AC: 15416 AN: 26122

East Asian (EAS) AF: 0.806 AC: 31983 AN: 39682

South Asian (SAS) AF: 0.665 AC: 57398 AN: 86252

European-Finnish (FIN) AF: 0.668 AC: 35700 AN: 53412

Middle Eastern (MID) AF: 0.711 AC: 4100 AN: 5766

European-Non Finnish (NFE) AF: 0.608 AC: 676365 AN: 1111650

Other (OTH) AF: 0.622 AC: 37555 AN: 60366

GnomAD4 genome AF: 0.624 AC: 94830 AN: 152020 Hom.: 29894 Cov.: 32 AF XY: 0.630 AC XY: 46780 AN XY: 74294

African (AFR) AF: 0.575 AC: 23840 AN: 41492

American (AMR) AF: 0.714 AC: 10884 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.587 AC: 2035 AN: 3466

East Asian (EAS) AF: 0.806 AC: 4175 AN: 5180

South Asian (SAS) AF: 0.674 AC: 3245 AN: 4818

European-Finnish (FIN) AF: 0.666 AC: 7035 AN: 10564

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.612 AC: 41552 AN: 67932

Other (OTH) AF: 0.633 AC: 1336 AN: 2110

Alfa AF: 0.623 Hom.: 115028

Bravo AF: 0.628

TwinsUK AF: 0.597 AC: 2212

ALSPAC AF: 0.605 AC: 2331

ESP6500AA AF: 0.586 AC: 2580

ESP6500EA AF: 0.610 AC: 5250

ExAC AF: 0.657 AC: 79723

Asia WGS AF: 0.707 AC: 2460 AN: 3478

EpiCase AF: 0.607

EpiControl AF: 0.616

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	Asphyxiating thoracic dystrophy 4 (2)
-	-	1	Jeune thoracic dystrophy;C0687120:Nephronophthisis (1)
-	-	1	Nephronophthisis 12 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Benign	0.064
Eigen_PC	Benign	-0.045
FATHMM_MKL	Benign	0.27	N
LIST_S2	Uncertain	0.97	D
MetaRNN	Benign	0.0000022	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		0.74
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.23
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.99	D
Vest4		0.21
MPC		0.21
ClinPred		0.037	T
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.074
gMVP		0.38
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1432273; hg19: chr2-166797646; COSMIC: COSV107292410;