rs137916

Positions:

• chr22-50053284-G-A

Variant summary

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

The NM_001350317.3(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 NM_001350317.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
TTLL8	NM_001350317.3	c.159+1950C>T		intron_variant		ENST00000433387.2
TTLL8	XM_024452172.1	c.159+1950C>T		intron_variant
TTLL8	XM_024452173.1	c.159+1950C>T		intron_variant
TTLL8	XM_047441179.1	c.159+1950C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTLL8	ENST00000433387.2	c.159+1950C>T		intron_variant		5	NM_001350317.3	P1

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

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.239

Gnomad4 ASJ AF: 0.222

Gnomad4 EAS AF: 0.260

Gnomad4 SAS AF: 0.271

Gnomad4 FIN AF: 0.275

Gnomad4 NFE AF: 0.262

Gnomad4 OTH AF: 0.207

Alfa AF: 0.248 Hom.: 4625

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs137916; hg19: chr22-50491713;