6-155256903-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_012454.4(TIAM2):​c.4888G>A​(p.Gly1630Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Consequence

TIAM2
NM_012454.4 missense

Scores

4
7
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.00
Variant links:
Genes affected
TIAM2 (HGNC:11806): (TIAM Rac1 associated GEF 2) This gene encodes a guanine nucleotide exchange factor. A highly similar mouse protein specifically activates ras-related C3 botulinum substrate 1, converting this Rho-like guanosine triphosphatase (GTPase) from a guanosine diphosphate-bound inactive state to a guanosine triphosphate-bound active state. The encoded protein may play a role in neural cell development. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]
TFB1M (HGNC:17037): (transcription factor B1, mitochondrial) The protein encoded by this gene is a dimethyltransferase that methylates the conserved stem loop of mitochondrial 12S rRNA. The encoded protein also is part of the basal mitochondrial transcription complex and is necessary for mitochondrial gene expression. The methylation and transcriptional activities of this protein are independent of one another. Variations in this gene may influence the severity of aminoglycoside-induced deafness (AID).[provided by RefSeq, Aug 2010]

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ACMG classification

Classification made for transcript

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=0.29867637).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TIAM2NM_012454.4 linkuse as main transcriptc.4888G>A p.Gly1630Arg missense_variant 27/27 ENST00000682666.1 NP_036586.3
TFB1MNM_016020.4 linkuse as main transcriptc.*933C>T 3_prime_UTR_variant 7/7 ENST00000367166.5 NP_057104.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TIAM2ENST00000682666.1 linkuse as main transcriptc.4888G>A p.Gly1630Arg missense_variant 27/27 NM_012454.4 ENSP00000507157 A2Q8IVF5-1
TFB1MENST00000367166.5 linkuse as main transcriptc.*933C>T 3_prime_UTR_variant 7/71 NM_016020.4 ENSP00000356134 P1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
37
GnomAD4 genome
Cov.:
31
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000151

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsNov 17, 2023The c.4888G>A (p.G1630R) alteration is located in exon 26 (coding exon 24) of the TIAM2 gene. This alteration results from a G to A substitution at nucleotide position 4888, causing the glycine (G) at amino acid position 1630 to be replaced by an arginine (R). 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
Uncertain
0.44
BayesDel_addAF
Uncertain
0.016
T
BayesDel_noAF
Benign
-0.21
CADD
Uncertain
24
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.030
T;.;.;.;T;.
Eigen
Pathogenic
0.73
Eigen_PC
Pathogenic
0.75
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.91
D;D;D;D;D;D
M_CAP
Benign
0.0071
T
MetaRNN
Benign
0.30
T;T;T;T;T;T
MetaSVM
Benign
-1.2
T
MutationAssessor
Uncertain
2.2
M;.;.;.;.;.
MutationTaster
Benign
1.0
D;D;D;D;D;D;D;D;D
PrimateAI
Uncertain
0.60
T
PROVEAN
Benign
-1.6
N;N;N;N;N;N
REVEL
Benign
0.14
Sift
Uncertain
0.0010
D;D;D;D;D;D
Sift4G
Uncertain
0.0040
D;D;D;D;D;D
Polyphen
0.96
D;D;D;.;P;.
Vest4
0.21
MutPred
0.30
Loss of sheet (P = 0.0181);.;.;.;.;.;
MVP
0.35
MPC
0.32
ClinPred
0.86
D
GERP RS
6.0
Varity_R
0.17
gMVP
0.19

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1234005986; hg19: chr6-155578037; API