1-83922435-G-C

Variant names:

• chr1-83922435-G-C
• rs10493741
• NM_024686.6:c.1143-1041C>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024686.6(TTLL7):​c.1143-1041C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 151,904 control chromosomes in the GnomAD database, including 19,224 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.49 (19224 hom., cov: 31)
• Consequence: TTLL7 NM_024686.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.548

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTLL7	NM_024686.6	c.1143-1041C>G		intron_variant	Intron 10 of 20	ENST00000260505.13	NP_078962.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTLL7	ENST00000260505.13	c.1143-1041C>G		intron_variant	Intron 10 of 20	2	NM_024686.6	ENSP00000260505.8

Frequencies

GnomAD3 genomes AF: 0.494 AC: 74955 AN: 151786 Hom.: 19219 Cov.: 31

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.287

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.560

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.500

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.494 AC: 74978 AN: 151904 Hom.: 19224 Cov.: 31 AF XY: 0.489 AC XY: 36286 AN XY: 74220

Gnomad4 AFR AF: 0.371

Gnomad4 AMR AF: 0.540

Gnomad4 ASJ AF: 0.530

Gnomad4 EAS AF: 0.286

Gnomad4 SAS AF: 0.375

Gnomad4 FIN AF: 0.560

Gnomad4 NFE AF: 0.570

Gnomad4 OTH AF: 0.495

Alfa AF: 0.387 Hom.: 1042

Bravo AF: 0.494

Asia WGS AF: 0.344 AC: 1195 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.4
DANN	Benign	0.49

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

LitVar

Other links and lift over

dbSNP: rs10493741; hg19: chr1-84388118;