1-83907521-G-A

Variant names:

• chr1-83907521-G-A
• rs774505633
• NM_024686.6:c.1927C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024686.6(TTLL7):​c.1927C>T​(p.Arg643Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000219 in 1,460,998 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R643G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: TTLL7 NM_024686.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.98
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3575065).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTLL7	NM_024686.6	c.1927C>T	p.Arg643Cys	missense_variant	Exon 16 of 21	ENST00000260505.13	NP_078962.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTLL7	ENST00000260505.13	c.1927C>T	p.Arg643Cys	missense_variant	Exon 16 of 21	2	NM_024686.6	ENSP00000260505.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000797 AC: 2 AN: 250862 AF XY: 0.0000148

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: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000219 AC: 32 AN: 1460998 Hom.: 0 Cov.: 31 AF XY: 0.0000206 AC XY: 15 AN XY: 726822

African (AFR) AF: 0.00 AC: 0 AN: 33412

American (AMR) AF: 0.00 AC: 0 AN: 44642

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26078

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.0000243 AC: 27 AN: 1111442

Other (OTH) AF: 0.0000829 AC: 5 AN: 60336

GnomAD4 genome Cov.: 32

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.40
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T
Eigen	Benign	0.066
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.7	L
PhyloP100		6.0
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.064
Sift	Benign	0.080	T
Sift4G	Benign	0.14	T
Polyphen		0.46	P
Vest4		0.56
MutPred		0.31		Loss of MoRF binding (P = 0.0068);
MVP		0.29
MPC		0.79
ClinPred		0.93	D
GERP RS		5.3
Varity_R		0.12
gMVP		0.58
Mutation Taster		=80/20	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: rs774505633; hg19: chr1-84373204;