rs772285722

Variant names:

• chr11-64223946-C-T
• rs772285722
• NM_001033678.4:c.692G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-64223946-C-T
• chr11-64223946-C-A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001033678.4(TRPT1):​c.692G>A​(p.Gly231Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,682 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TRPT1 NM_001033678.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0780
• Publications: 2 publications found

Genes affected

TRPT1 (HGNC:20316): (tRNA phosphotransferase 1) Predicted to enable tRNA 2'-phosphotransferase activity. Predicted to be involved in tRNA splicing, via endonucleolytic cleavage and ligation. Predicted to act upstream of or within regulation of protein kinase activity. [provided by Alliance of Genome Resources, Apr 2022]

FERMT3 (HGNC:23151): (FERM domain containing kindlin 3) Kindlins are a small family of proteins that mediate protein-protein interactions involved in integrin activation and thereby have a role in cell adhesion, migration, differentiation, and proliferation. The protein encoded by this gene has a key role in the regulation of hemostasis and thrombosis. This protein may also help maintain the membrane skeleton of erythrocytes. Mutations in this gene cause the autosomal recessive leukocyte adhesion deficiency syndrome-III (LAD-III). Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jan 2010]

FERMT3 Gene-Disease associations (from GenCC):

• leukocyte adhesion deficiency 3

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet, ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11729509).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001033678.4. 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
	TRPT1	NM_001033678.4	MANE Select	c.692G>A	p.Gly231Asp	missense	Exon 8 of 8	NP_001028850.2	Q86TN4-1
	TRPT1	NM_001160389.2		c.698G>A	p.Gly233Asp	missense	Exon 8 of 8	NP_001153861.1	Q86TN4-4
	TRPT1	NM_001160393.1		c.695G>A	p.Gly232Asp	missense	Exon 7 of 7	NP_001153865.1	Q86TN4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPT1	ENST00000317459.11	TSL:1 MANE Select	c.692G>A	p.Gly231Asp	missense	Exon 8 of 8	ENSP00000314073.6	Q86TN4-1
	TRPT1	ENST00000394547.7	TSL:1	c.545G>A	p.Gly182Asp	missense	Exon 7 of 7	ENSP00000378051.3	Q86TN4-2
	TRPT1	ENST00000394546.6	TSL:5	c.698G>A	p.Gly233Asp	missense	Exon 8 of 8	ENSP00000378050.2	Q86TN4-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251380 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461682 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727154

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111876

Other (OTH) AF: 0.0000166 AC: 1 AN: 60384

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	14
DANN	Benign	0.88
DEOGEN2	Benign	0.0069	T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.078
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.89	N
REVEL	Benign	0.050
Sift	Benign	0.042	D
Sift4G	Benign	0.23	T
Polyphen		0.65	P
Vest4		0.20
MutPred		0.098		Gain of solvent accessibility (P = 0.0281)
MVP		0.35
MPC		0.30
ClinPred		0.34	T
GERP RS		-1.4
Varity_R		0.092
gMVP		0.41
Mutation Taster		=90/10	polymorphism

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: rs772285722; hg19: chr11-63991418;