rs10804990

Positions:

• chr4-6917934-G-A
• chr4-6917934-G-T

Variant summary

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

The ENST00000409757.9(TBC1D14):​c.-17-5439G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 151,978 control chromosomes in the GnomAD database, including 23,694 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 0.54 (23694 hom., cov: 32)
• Consequence: TBC1D14 ENST00000409757.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.309

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D14	NM_020773.3	c.-17-5439G>A		intron_variant		ENST00000409757.9	NP_065824.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBC1D14	ENST00000409757.9	c.-17-5439G>A		intron_variant		1	NM_020773.3	ENSP00000386921
TBC1D14	ENST00000427736.1	c.-17-5439G>A		intron_variant		2		ENSP00000411760
TBC1D14	ENST00000444368.1	c.-17-5439G>A		intron_variant		3		ENSP00000414951
TBC1D14	ENST00000448507.5	c.-17-5439G>A		intron_variant		5		ENSP00000404041

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82696 AN: 151860 Hom.: 23681 Cov.: 32

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.688

Gnomad EAS AF: 0.678

Gnomad SAS AF: 0.740

Gnomad FIN AF: 0.595

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.580

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

GnomAD4 genome AF: 0.544 AC: 82729 AN: 151978 Hom.: 23694 Cov.: 32 AF XY: 0.549 AC XY: 40790 AN XY: 74274

Gnomad4 AFR AF: 0.359

Gnomad4 AMR AF: 0.555

Gnomad4 ASJ AF: 0.688

Gnomad4 EAS AF: 0.678

Gnomad4 SAS AF: 0.740

Gnomad4 FIN AF: 0.595

Gnomad4 NFE AF: 0.612

Gnomad4 OTH AF: 0.582

Alfa AF: 0.603 Hom.: 37615

Bravo AF: 0.529

Asia WGS AF: 0.672 AC: 2339 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	3.9
DANN	Benign	0.73

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

Publications

LitVar

Other links and lift over

dbSNP: rs10804990; hg19: chr4-6919661;