ENST00000433387.2:c.159+1950C>T

Variant names:

• chr22-50053284-G-A
• rs137916
• ENST00000433387.2:c.159+1950C>T

Variant summary

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

The ENST00000433387.2(TTLL8):​c.159+1950C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 150,340 control chromosomes in the GnomAD database, including 3,887 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 0.22 (3887 hom., cov: 32)
• Consequence: TTLL8 ENST00000433387.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• Publications: 5 publications found

Genes affected

TTLL8 (HGNC:34000): (tubulin tyrosine ligase like 8) Predicted to enable protein-glycine ligase activity, initiating. Predicted to be involved in protein polyglycylation. Predicted to act upstream of or within cilium assembly. Predicted to be located in axoneme and microtubule cytoskeleton. [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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTLL8	NM_001350317.3	c.159+1950C>T		intron_variant	Intron 3 of 13		NP_001337246.1
TTLL8	XM_024452172.1	c.159+1950C>T		intron_variant	Intron 3 of 13		XP_024307940.1
TTLL8	XM_024452173.1	c.159+1950C>T		intron_variant	Intron 3 of 13		XP_024307941.1
TTLL8	XM_047441179.1	c.159+1950C>T		intron_variant	Intron 3 of 10		XP_047297135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTLL8	ENST00000433387.2	c.159+1950C>T		intron_variant	Intron 3 of 13	5		ENSP00000392252.2

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33081 AN: 150278 Hom.: 3883 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.220 AC: 33096 AN: 150340 Hom.: 3887 Cov.: 32 AF XY: 0.221 AC XY: 16243 AN XY: 73390

African (AFR) AF: 0.117 AC: 4810 AN: 40956

American (AMR) AF: 0.239 AC: 3615 AN: 15118

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 769 AN: 3468

East Asian (EAS) AF: 0.260 AC: 1340 AN: 5154

South Asian (SAS) AF: 0.271 AC: 1300 AN: 4794

European-Finnish (FIN) AF: 0.275 AC: 2692 AN: 9786

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.262 AC: 17788 AN: 67770

Other (OTH) AF: 0.207 AC: 433 AN: 2090

Alfa AF: 0.242 Hom.: 6582

Bravo AF: 0.214

Asia WGS AF: 0.241 AC: 839 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.050
DANN	Benign	0.80
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs137916; hg19: chr22-50491713;