chr3-36831581-C-T

Position:

• chr3-36831581-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001329998.2(TRANK1):​c.8002G>A​(p.Val2668Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,392 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: TRANK1 NM_001329998.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.442

Genes affected

TRANK1 (HGNC:29011): (tetratricopeptide repeat and ankyrin repeat containing 1) Predicted to enable ATP binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14897731).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRANK1	NM_001329998.2	c.8002G>A	p.Val2668Ile	missense_variant	22/24	ENST00000645898.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRANK1	ENST00000645898.2	c.8002G>A	p.Val2668Ile	missense_variant	22/24		NM_001329998.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000806 AC: 2 AN: 248174 Hom.: 0 AF XY: 0.0000149 AC XY: 2 AN XY: 134672

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000890

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461392 Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8 AN XY: 726946

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000899

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.035	T;.
Eigen	Benign	0.14
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.68	T;T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.3	M;.
MutationTaster	Benign	0.80	N;N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.17	N;.
REVEL	Benign	0.10
Sift	Uncertain	0.010	D;.
Sift4G	Benign	0.14	T;.
Polyphen		0.88	P;.
Vest4		0.13
MutPred		0.25		Loss of sheet (P = 0.0228);.;
MVP		0.20
MPC		0.16
ClinPred		0.74	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.077
gMVP		0.13

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: rs1290183229; hg19: chr3-36873072;