rs16839553

Variant names:

• chr4-7016458-G-A
• rs16839553
• NM_020773.3:c.1757+1901G>A

Variant summary

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

The NM_020773.3(TBC1D14):​c.1757+1901G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.051 in 152,332 control chromosomes in the GnomAD database, including 443 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 0.051 (443 hom., cov: 34)
• Consequence: TBC1D14 NM_020773.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66
• Publications: 4 publications found

Genes affected

TBC1D14 (HGNC:29246): (TBC1 domain family member 14) Enables protein kinase binding activity. Involved in negative regulation of autophagy; recycling endosome to Golgi transport; and regulation of autophagosome assembly. Located in several cellular components, including Golgi apparatus; autophagosome; and recycling endosome. [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 (AFR) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBC1D14	NM_020773.3	c.1757+1901G>A		intron_variant	Intron 12 of 13	ENST00000409757.9	NP_065824.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBC1D14	ENST00000409757.9	c.1757+1901G>A		intron_variant	Intron 12 of 13	1	NM_020773.3	ENSP00000386921.4

Frequencies

GnomAD3 genomes AF: 0.0509 AC: 7754 AN: 152214 Hom.: 440 Cov.: 34

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.0286

Gnomad AMR AF: 0.0260

Gnomad ASJ AF: 0.0337

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0193

Gnomad FIN AF: 0.00179

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0177

Gnomad OTH AF: 0.0420

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

GnomAD4 genome AF: 0.0510 AC: 7775 AN: 152332 Hom.: 443 Cov.: 34 AF XY: 0.0501 AC XY: 3730 AN XY: 74486

African (AFR) AF: 0.140 AC: 5816 AN: 41556

American (AMR) AF: 0.0260 AC: 398 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0337 AC: 117 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.0193 AC: 93 AN: 4826

European-Finnish (FIN) AF: 0.00179 AC: 19 AN: 10628

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0177 AC: 1205 AN: 68046

Other (OTH) AF: 0.0411 AC: 87 AN: 2116

Alfa AF: 0.0697 Hom.: 241

Bravo AF: 0.0558

Asia WGS AF: 0.0130 AC: 45 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	0.16
DANN	Benign	0.82
PhyloP100		-1.7
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: rs16839553; hg19: chr4-7018185;