NM_014640.5:c.1661+911T>G

Variant names:

• chr2-218741495-T-G
• rs1554622
• NM_014640.5:c.1661+911T>G

Variant summary

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

The NM_014640.5(TTLL4):​c.1661+911T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 152,026 control chromosomes in the GnomAD database, including 23,168 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 0.53 (23168 hom., cov: 32)
• Consequence: TTLL4 NM_014640.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.273
• Publications: 22 publications found

Genes affected

TTLL4 (HGNC:28976): (tubulin tyrosine ligase like 4) 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 act upstream of or within regulation of blastocyst development. Predicted to be located in cytosol. 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTLL4	NM_014640.5	c.1661+911T>G		intron_variant	Intron 5 of 19	ENST00000392102.6	NP_055455.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTLL4	ENST00000392102.6	c.1661+911T>G		intron_variant	Intron 5 of 19	1	NM_014640.5	ENSP00000375951.1
TTLL4	ENST00000258398.8	c.1661+911T>G		intron_variant	Intron 3 of 17	2		ENSP00000258398.4
TTLL4	ENST00000442769.5	c.1661+911T>G		intron_variant	Intron 5 of 18	5		ENSP00000396555.1
TTLL4	ENST00000457313.5	c.1166+911T>G		intron_variant	Intron 4 of 18	2		ENSP00000393332.1

Frequencies

GnomAD3 genomes AF: 0.533 AC: 80951 AN: 151908 Hom.: 23132 Cov.: 32

Gnomad AFR AF: 0.733

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.508

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

GnomAD4 genome AF: 0.533 AC: 81037 AN: 152026 Hom.: 23168 Cov.: 32 AF XY: 0.526 AC XY: 39140 AN XY: 74340

African (AFR) AF: 0.733 AC: 30395 AN: 41452

American (AMR) AF: 0.464 AC: 7091 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.432 AC: 1497 AN: 3466

East Asian (EAS) AF: 0.141 AC: 728 AN: 5176

South Asian (SAS) AF: 0.338 AC: 1630 AN: 4824

European-Finnish (FIN) AF: 0.523 AC: 5517 AN: 10554

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

European-Non Finnish (NFE) AF: 0.480 AC: 32625 AN: 67970

Other (OTH) AF: 0.507 AC: 1066 AN: 2102

Alfa AF: 0.458 Hom.: 10146

Bravo AF: 0.540

Asia WGS AF: 0.290 AC: 1011 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	8.8
DANN	Benign	0.78
PhyloP100		0.27
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1554622; hg19: chr2-219606218;