dbSNP rs1197366312: TTLL7:p.Arg814Cys (chr1-83883066-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_024686.6(TTLL7):c.2440C>T(p.Arg814Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000116 in 1,460,340 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

TTLL7
NM_024686.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.34

Publications

0 publications found

Variant links:

Genes affected

TTLL7 (HGNC:26242): (tubulin tyrosine ligase like 7) Enables alpha-tubulin binding activity; beta-tubulin binding activity; and tubulin-glutamic acid ligase activity. Involved in protein polyglutamylation. Predicted to be located in 9+0 non-motile cilium and ciliary basal body. Predicted to be active in cilium. [provided by Alliance of Genome Resources, Apr 2022]

TTLL7 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTLL7	NM_024686.6 link	c.2440C>T	p.Arg814Cys	missense_variant	Exon 20 of 21	ENST00000260505.13	NP_078962.4	Q6ZT98-1
TTLL7	NM_001350214.2 link	c.2440C>T	p.Arg814Cys	missense_variant	Exon 21 of 22		NP_001337143.1
TTLL7	NM_001350215.2 link	c.2359C>T	p.Arg787Cys	missense_variant	Exon 19 of 20		NP_001337144.1
TTLL7	XM_047430691.1 link	c.1705C>T	p.Arg569Cys	missense_variant	Exon 14 of 15		XP_047286647.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTLL7	ENST00000260505.13 link	c.2440C>T	p.Arg814Cys	missense_variant	Exon 20 of 21	2	NM_024686.6	ENSP00000260505.8		Q6ZT98-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000802

AC:

AN:

249466

AF XY:

0.00000742

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000889

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000116

AC:

AN:

1460340

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726486

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33348

American (AMR)

AF:

0.0000224

AC:

AN:

44554

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26078

East Asian (EAS)

AF:

0.00

AC:

AN:

39678

South Asian (SAS)

AF:

0.00

AC:

AN:

86114

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

0.0000144

AC:

AN:

1111118

Other (OTH)

AF:

0.00

AC:

AN:

60310

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 06, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.2440C>T (p.R814C) alteration is located in exon 20 (coding exon 19) of the TTLL7 gene. This alteration results from a C to T substitution at nucleotide position 2440, causing the arginine (R) at amino acid position 814 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.018

BayesDel_noAF

Benign

-0.26

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.23

Eigen

Pathogenic

0.78

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Uncertain

0.94

LIST_S2

Pathogenic

0.97

M_CAP

Benign

0.022

MetaRNN

Uncertain

0.52

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.5

PhyloP100

6.3

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-3.5

REVEL

Uncertain

0.37

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.54

MutPred

0.54

Gain of catalytic residue at L815 (P = 0.0238);

MVP

0.38

MPC

1.7

ClinPred

0.99

GERP RS

5.7

Varity_R

0.46

gMVP

0.86

Mutation Taster

=69/31

polymorphism

(source)

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

Publications

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rs1197366312

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over