NM_024753.5:c.*1105G>T

Variant names:

• chr2-165873650-C-A
• rs6756388
• NM_024753.5:c.*1105G>T

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.*1105G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 151,918 control chromosomes in the GnomAD database, including 5,150 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (5150 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: TTC21B NM_024753.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.364
• 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 Gene-Disease associations (from GenCC):

• asphyxiating thoracic dystrophy 4

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• nephronophthisis 12

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
• Jeune syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• nephronophthisis 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 2-165873650-C-A is Benign according to our data. Variant chr2-165873650-C-A is described in ClinVar as Benign. ClinVar VariationId is 331798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.315 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.*1105G>T		3_prime_UTR	Exon 29 of 29	NP_079029.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC21B	ENST00000243344.8	TSL:1 MANE Select	c.*1105G>T		3_prime_UTR	Exon 29 of 29	ENSP00000243344.7	Q7Z4L5-1
	TTC21B	ENST00000959804.1		c.*1105G>T		3_prime_UTR	Exon 28 of 28	ENSP00000629863.1
	TTC21B	ENST00000679799.1		c.3806-2630G>T		intron	N/A	ENSP00000505208.1	A0A494C0N4

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36266 AN: 151800 Hom.: 5148 Cov.: 32

Gnomad AFR AF: 0.0864

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.289

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.239 AC: 36270 AN: 151918 Hom.: 5150 Cov.: 32 AF XY: 0.236 AC XY: 17544 AN XY: 74236

African (AFR) AF: 0.0862 AC: 3575 AN: 41452

American (AMR) AF: 0.258 AC: 3931 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1343 AN: 3470

East Asian (EAS) AF: 0.128 AC: 662 AN: 5152

South Asian (SAS) AF: 0.267 AC: 1285 AN: 4810

European-Finnish (FIN) AF: 0.264 AC: 2780 AN: 10534

Middle Eastern (MID) AF: 0.408 AC: 119 AN: 292

European-Non Finnish (NFE) AF: 0.319 AC: 21647 AN: 67928

Other (OTH) AF: 0.287 AC: 604 AN: 2106

Alfa AF: 0.268 Hom.: 797

Bravo AF: 0.233

Asia WGS AF: 0.185 AC: 645 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Asphyxiating thoracic dystrophy 4 (1)
-	-	1	Nephronophthisis 12 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.94
DANN	Benign	0.76
PhyloP100		-0.36
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: rs6756388; hg19: chr2-166730160;