8-123093726-G-A

Position:

• chr8-123093726-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_145647.4(TBC1D31):​c.655G>A​(p.Val219Met) variant causes a missense change. The variant allele was found at a frequency of 0.000000697 in 1,435,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: TBC1D31 NM_145647.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.36

Genes affected

TBC1D31 (HGNC:30888): (TBC1 domain family member 31) Located in centrosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34895796).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D31	NM_145647.4	c.655G>A	p.Val219Met	missense_variant	5/22	ENST00000287380.6	NP_663622.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBC1D31	ENST00000287380.6	c.655G>A	p.Val219Met	missense_variant	5/22	1	NM_145647.4	ENSP00000287380	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.97e-7 AC: 1 AN: 1435724 Hom.: 0 Cov.: 29 AF XY: 0.00000140 AC XY: 1 AN XY: 713664

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000123

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 30, 2021

The c.655G>A (p.V219M) alteration is located in exon 5 (coding exon 5) of the TBC1D31 gene. This alteration results from a G to A substitution at nucleotide position 655, causing the valine (V) at amino acid position 219 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Uncertain	0.032	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0040	T;.;T;.;T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.98	D;D;D;D;D
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.35	T;T;T;T;T
MetaSVM	Benign	-0.37	T
MutationAssessor	Uncertain	2.2	M;M;.;.;.
MutationTaster	Benign	0.99	D;D;D;D;D;D
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.1	N;N;N;N;N
REVEL	Benign	0.15
Sift	Uncertain	0.025	D;D;D;D;T
Sift4G	Uncertain	0.038	D;D;D;D;D
Polyphen		0.99	D;.;.;.;.
Vest4		0.52
MutPred		0.47		Loss of methylation at K218 (P = 0.0438);Loss of methylation at K218 (P = 0.0438);.;.;.;
MVP		0.79
MPC		0.32
ClinPred		0.85	D
GERP RS		5.7
Varity_R		0.17
gMVP		0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-124105966;