3-36831425-G-T

Position:

• chr3-36831425-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001329998.2(TRANK1):​c.8158C>A​(p.Gln2720Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 6.8e-7 (0 hom.)
• Consequence: TRANK1 NM_001329998.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.41

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.044501156).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRANK1	NM_001329998.2	c.8158C>A	p.Gln2720Lys	missense_variant	22/24	ENST00000645898.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRANK1	ENST00000645898.2	c.8158C>A	p.Gln2720Lys	missense_variant	22/24		NM_001329998.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000405 AC: 1 AN: 246922 Hom.: 0 AF XY: 0.00000747 AC XY: 1 AN XY: 133902

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: 0.00000893

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460746 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726538

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: 9.00e-7

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

Jun 17, 2022

The c.8026C>A (p.Q2676K) alteration is located in exon 21 (coding exon 21) of the TRANK1 gene. This alteration results from a C to A substitution at nucleotide position 8026, causing the glutamine (Q) at amino acid position 2676 to be replaced by a lysine (K). 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	0.087
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	18
DANN	Benign	0.60
DEOGEN2	Benign	0.031	T;.
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.72	T;T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.045	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.61	N;.
REVEL	Benign	0.071
Sift	Benign	0.56	T;.
Sift4G	Benign	1.0	T;.
Polyphen		0.0010	B;.
Vest4		0.25
MutPred		0.26		Gain of glycosylation at S2674 (P = 0.0054);.;
MVP		0.092
MPC		0.23
ClinPred		0.072	T
GERP RS		4.6
Varity_R		0.16
gMVP		0.55

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: rs1224202339; hg19: chr3-36872916;