NM_001330348.2:c.2827+2774C>T

Variant names:

• chr2-101018907-G-A
• rs56291532
• NM_001330348.2:c.2827+2774C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0440
• Publications: 2 publications found

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]

RPL31 Gene-Disease associations (from GenCC):

• Diamond-Blackfan anemia

  Inheritance: AD Classification: MODERATE Submitted by: PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1183797.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330348.2. 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
	TBC1D8	NM_001330348.2	MANE Select	c.2827+2774C>T		intron	N/A	NP_001317277.1	J3KQ40
	TBC1D8	NM_001102426.3		c.2782+2774C>T		intron	N/A	NP_001095896.1	O95759-1
	RPL31	NM_001098577.3		c.347-91G>A		intron	N/A	NP_001092047.1	P62899-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D8	ENST00000409318.2	TSL:5 MANE Select	c.2827+2774C>T		intron	N/A	ENSP00000386856.1	J3KQ40
	TBC1D8	ENST00000376840.8	TSL:1	c.2782+2774C>T		intron	N/A	ENSP00000366036.4	O95759-1
	TBC1D8	ENST00000870702.1		c.2836+2774C>T		intron	N/A	ENSP00000540761.1

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

African (AFR) AF: 0.0633 AC: 1997 AN: 31548

American (AMR) AF: 0.0696 AC: 2498 AN: 35872

Ashkenazi Jewish (ASJ) AF: 0.0573 AC: 1401 AN: 24468

East Asian (EAS) AF: 0.000493 AC: 18 AN: 36546

South Asian (SAS) AF: 0.0653 AC: 5053 AN: 77344

European-Finnish (FIN) AF: 0.152 AC: 7490 AN: 49176

Middle Eastern (MID) AF: 0.0612 AC: 340 AN: 5556

European-Non Finnish (NFE) AF: 0.140 AC: 146668 AN: 1047894

Other (OTH) AF: 0.105 AC: 5963 AN: 56566

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

African (AFR) AF: 0.0657 AC: 2728 AN: 41548

American (AMR) AF: 0.0966 AC: 1477 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0550 AC: 191 AN: 3472

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5186

South Asian (SAS) AF: 0.0597 AC: 288 AN: 4826

European-Finnish (FIN) AF: 0.153 AC: 1621 AN: 10594

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.135 AC: 9156 AN: 68012

Other (OTH) AF: 0.108 AC: 228 AN: 2114

Alfa AF: 0.111 Hom.: 134

Bravo AF: 0.0983

Asia WGS AF: 0.0300 AC: 108 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.56
DANN	Benign	0.76
PhyloP100		0.044
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: rs56291532; hg19: chr2-101635369;