2-101018907-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001330348.2(TBC1D8):c.2827+2774C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 1,517,224 control chromosomes in the GnomAD database, including 12,921 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (948 hom., cov: 33)
  • Exomes 𝑓: 0.13 (11973 hom.)
• Consequence: TBC1D8 NM_001330348.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0440

Genes affected

TBC1D8 (HGNC:17791): (TBC1 domain family member 8) Predicted to enable GTPase activator activity. Predicted to be involved in activation of GTPase activity and intracellular protein transport. Predicted to be located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

RPL31 (HGNC:10334): (ribosomal protein L31) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 60S subunit. The protein belongs to the L31E family of ribosomal proteins. It is located in the cytoplasm. Higher levels of expression of this gene in familial adenomatous polyps compared to matched normal tissues have been observed. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 2-101018907-G-A is Benign according to our data. Variant chr2-101018907-G-A is described in ClinVar as [Benign]. Clinvar id is 1183797.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBC1D8	NM_001330348.2	c.2827+2774C>T		intron_variant		ENST00000409318.2
RPL31	NM_001098577.3	c.347-91G>A		intron_variant
TBC1D8	NM_001102426.3	c.2782+2774C>T		intron_variant
TBC1D8	NR_138475.2	n.2793+2774C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBC1D8	ENST00000409318.2	c.2827+2774C>T		intron_variant		5	NM_001330348.2	A1

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15821 AN: 152136 Hom.: 947 Cov.: 33

Gnomad AFR AF: 0.0655

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.0968

Gnomad ASJ AF: 0.0550

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0598

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.109

GnomAD4 exome AF: 0.126 AC: 171428 AN: 1364970 Hom.: 11973 AF XY: 0.123 AC XY: 83138 AN XY: 673700

Gnomad4 AFR exome AF: 0.0633

Gnomad4 AMR exome AF: 0.0696

Gnomad4 ASJ exome AF: 0.0573

Gnomad4 EAS exome AF: 0.000493

Gnomad4 SAS exome AF: 0.0653

Gnomad4 FIN exome AF: 0.152

Gnomad4 NFE exome AF: 0.140

Gnomad4 OTH exome AF: 0.105

GnomAD4 genome AF: 0.104 AC: 15835 AN: 152254 Hom.: 948 Cov.: 33 AF XY: 0.104 AC XY: 7748 AN XY: 74454

Gnomad4 AFR AF: 0.0657

Gnomad4 AMR AF: 0.0966

Gnomad4 ASJ AF: 0.0550

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.0597

Gnomad4 FIN AF: 0.153

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.108

Alfa AF: 0.113 Hom.: 134

Bravo AF: 0.0983

Asia WGS AF: 0.0300 AC: 108 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 17, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.56
Dann	Benign	0.76

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: rs56291532; hg19: chr2-101635369;