chr4-6917934-G-A

Variant names:

• chr4-6917934-G-A
• rs10804990
• NM_020773.3:c.-17-5439G>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.-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 NM_020773.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.309
• Publications: 7 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=-0.63).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020773.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D14	NM_020773.3	MANE Select	c.-17-5439G>A		intron	N/A	NP_065824.2	Q9P2M4-1
	TBC1D14	NM_001113361.2		c.-17-5439G>A		intron	N/A	NP_001106832.1	Q9P2M4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D14	ENST00000409757.9	TSL:1 MANE Select	c.-17-5439G>A		intron	N/A	ENSP00000386921.4	Q9P2M4-1
	TBC1D14	ENST00000953325.1		c.-18G>A		splice_region	Exon 1 of 14	ENSP00000623384.1
	TBC1D14	ENST00000953325.1		c.-18G>A		5_prime_UTR	Exon 1 of 14	ENSP00000623384.1

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

African (AFR) AF: 0.359 AC: 14858 AN: 41412

American (AMR) AF: 0.555 AC: 8472 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.688 AC: 2386 AN: 3468

East Asian (EAS) AF: 0.678 AC: 3497 AN: 5160

South Asian (SAS) AF: 0.740 AC: 3569 AN: 4820

European-Finnish (FIN) AF: 0.595 AC: 6282 AN: 10556

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.612 AC: 41646 AN: 67998

Other (OTH) AF: 0.582 AC: 1224 AN: 2104

Alfa AF: 0.594 Hom.: 45632

Bravo AF: 0.529

Asia WGS AF: 0.672 AC: 2339 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	3.9
DANN	Benign	0.73
PhyloP100		0.31
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: rs10804990; hg19: chr4-6919661;