NM_012454.4:c.4888G>A

Variant names:

• chr6-155256903-G-A
• rs1234005986
• NM_012454.4:c.4888G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.00
• Publications: 0 publications found

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]

ENSG00000235381 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29867637).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012454.4. 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
	TIAM2	NM_012454.4	MANE Select	c.4888G>A	p.Gly1630Arg	missense	Exon 27 of 27	NP_036586.3
	TFB1M	NM_016020.4	MANE Select	c.*933C>T		3_prime_UTR	Exon 7 of 7	NP_057104.2	E5KTM5
	TIAM2	NM_001384546.1		c.4888G>A	p.Gly1630Arg	missense	Exon 27 of 27	NP_001371475.1	Q8IVF5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIAM2	ENST00000682666.1	MANE Select	c.4888G>A	p.Gly1630Arg	missense	Exon 27 of 27	ENSP00000507157.1	Q8IVF5-1
	TIAM2	ENST00000456877.6	TSL:1	c.2824G>A	p.Gly942Arg	missense	Exon 21 of 21	ENSP00000407183.2	Q8IVF5-4
	TIAM2	ENST00000275246.11	TSL:1	c.1663G>A	p.Gly555Arg	missense	Exon 13 of 13	ENSP00000275246.7	Q8IVF5-3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000151

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	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
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		6.0
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.14
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.96	D
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
Mutation Taster		=73/27	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: rs1234005986; hg19: chr6-155578037;