rs10465746

Variant names:

• chr1-83921949-T-G
• rs10465746
• NM_024686.6:c.1143-555A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024686.6(TTLL7):​c.1143-555A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 151,948 control chromosomes in the GnomAD database, including 15,863 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 0.44 (15863 hom., cov: 32)
• Consequence: TTLL7 NM_024686.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.564
• Publications: 4 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.532 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTLL7	NM_024686.6	MANE Select	c.1143-555A>C		intron	N/A	NP_078962.4
	TTLL7	NM_001350214.2		c.1143-555A>C		intron	N/A	NP_001337143.1
	TTLL7	NM_001350215.2		c.1062-555A>C		intron	N/A	NP_001337144.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTLL7	ENST00000260505.13	TSL:2 MANE Select	c.1143-555A>C		intron	N/A	ENSP00000260505.8
	TTLL7	ENST00000474957.5	TSL:1	n.198-555A>C		intron	N/A	ENSP00000434146.1
	TTLL7	ENST00000477524.5	TSL:1	n.1481-555A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66601 AN: 151830 Hom.: 15853 Cov.: 32

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.537

Gnomad OTH AF: 0.445

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

GnomAD4 genome AF: 0.438 AC: 66625 AN: 151948 Hom.: 15863 Cov.: 32 AF XY: 0.435 AC XY: 32296 AN XY: 74236

African (AFR) AF: 0.256 AC: 10630 AN: 41446

American (AMR) AF: 0.501 AC: 7641 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.470 AC: 1632 AN: 3472

East Asian (EAS) AF: 0.281 AC: 1448 AN: 5154

South Asian (SAS) AF: 0.355 AC: 1714 AN: 4824

European-Finnish (FIN) AF: 0.537 AC: 5662 AN: 10548

Middle Eastern (MID) AF: 0.322 AC: 94 AN: 292

European-Non Finnish (NFE) AF: 0.537 AC: 36468 AN: 67948

Other (OTH) AF: 0.440 AC: 929 AN: 2110

Alfa AF: 0.435 Hom.: 9872

Bravo AF: 0.436

Asia WGS AF: 0.323 AC: 1122 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.6
DANN	Benign	0.66
PhyloP100		0.56
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: rs10465746; hg19: chr1-84387632;