1-83922435-G-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024686.6. 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
	TTLL7	NM_024686.6	MANE Select	c.1143-1041C>G		intron	N/A	NP_078962.4
	TTLL7	NM_001350214.2		c.1143-1041C>G		intron	N/A	NP_001337143.1	Q6ZT98-1
	TTLL7	NM_001350215.2		c.1062-1041C>G		intron	N/A	NP_001337144.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTLL7	ENST00000260505.13	TSL:2 MANE Select	c.1143-1041C>G		intron	N/A	ENSP00000260505.8	Q6ZT98-1
	TTLL7	ENST00000474957.5	TSL:1	n.198-1041C>G		intron	N/A	ENSP00000434146.1	F2Z2J7
	TTLL7	ENST00000477524.5	TSL:1	n.1481-1041C>G		intron	N/A

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

African (AFR) AF: 0.371 AC: 15379 AN: 41440

American (AMR) AF: 0.540 AC: 8230 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.530 AC: 1836 AN: 3464

East Asian (EAS) AF: 0.286 AC: 1474 AN: 5152

South Asian (SAS) AF: 0.375 AC: 1806 AN: 4810

European-Finnish (FIN) AF: 0.560 AC: 5918 AN: 10562

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.570 AC: 38732 AN: 67920

Other (OTH) AF: 0.495 AC: 1043 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.4
DANN	Benign	0.49
PhyloP100		-0.55
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: rs10493741; hg19: chr1-84388118;