NM_031949.5:c.48-1958G>C

Variant names:

• chr6-167336689-G-C
• rs3010556
• NM_031949.5:c.48-1958G>C

Variant summary

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

The NM_031949.5(TTLL2):​c.48-1958G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.552 in 151,812 control chromosomes in the GnomAD database, including 23,549 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 0.55 (23549 hom., cov: 30)
• Consequence: TTLL2 NM_031949.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.776
• Publications: 3 publications found

Genes affected

TTLL2 (HGNC:21211): (tubulin tyrosine ligase like 2) Predicted to enable tubulin binding activity and tubulin-glutamic acid ligase activity. Predicted to be involved in microtubule cytoskeleton organization and protein polyglutamylation. 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTLL2	NM_031949.5	c.48-1958G>C		intron_variant	Intron 1 of 2	ENST00000239587.10	NP_114155.4
TTLL2	NM_001410948.1	c.-15-3416G>C		intron_variant	Intron 1 of 1		NP_001397877.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTLL2	ENST00000239587.10	c.48-1958G>C		intron_variant	Intron 1 of 2	1	NM_031949.5	ENSP00000239587.5
TTLL2	ENST00000515138.1	n.48-1958G>C		intron_variant	Intron 1 of 5	1		ENSP00000424130.1
TTLL2	ENST00000649884.1	c.-15-3416G>C		intron_variant	Intron 1 of 1			ENSP00000497040.1
TTLL2	ENST00000512917.1	n.*276-1958G>C		intron_variant	Intron 2 of 2	4		ENSP00000423198.1

Frequencies

GnomAD3 genomes AF: 0.552 AC: 83716 AN: 151694 Hom.: 23531 Cov.: 30

Gnomad AFR AF: 0.447

Gnomad AMI AF: 0.724

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.759

Gnomad SAS AF: 0.722

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.666

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.571

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

GnomAD4 genome AF: 0.552 AC: 83771 AN: 151812 Hom.: 23549 Cov.: 30 AF XY: 0.558 AC XY: 41410 AN XY: 74206

African (AFR) AF: 0.447 AC: 18473 AN: 41324

American (AMR) AF: 0.525 AC: 8011 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.564 AC: 1955 AN: 3464

East Asian (EAS) AF: 0.759 AC: 3894 AN: 5132

South Asian (SAS) AF: 0.724 AC: 3478 AN: 4804

European-Finnish (FIN) AF: 0.618 AC: 6523 AN: 10552

Middle Eastern (MID) AF: 0.654 AC: 191 AN: 292

European-Non Finnish (NFE) AF: 0.579 AC: 39373 AN: 67952

Other (OTH) AF: 0.575 AC: 1213 AN: 2110

Alfa AF: 0.422 Hom.: 1175

Bravo AF: 0.536

Asia WGS AF: 0.726 AC: 2524 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.20
DANN	Benign	0.57
PhyloP100		-0.78
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: rs3010556; hg19: chr6-167750177;