6-155256996-AGT-CGG

Variant names:

• chr6-155256996-AGT-CGG
• NM_012454.4:c.4981_4983delAGTinsCGG
• TIAM2 p.Ser1661Arg

Variant summary

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

The NM_012454.4(TIAM2):​c.4981_4983delAGTinsCGG​(p.Ser1661Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: TIAM2 NM_012454.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.19
• 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]

ACMG classification

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

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.4981_4983delAGTinsCGG	p.Ser1661Arg	missense	N/A	NP_036586.3
	TFB1M	NM_016020.4	MANE Select	c.*838_*840delACTinsCCG		3_prime_UTR	Exon 7 of 7	NP_057104.2	E5KTM5
	TIAM2	NM_001384546.1		c.4981_4983delAGTinsCGG	p.Ser1661Arg	missense	N/A	NP_001371475.1	Q8IVF5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIAM2	ENST00000682666.1	MANE Select	c.4981_4983delAGTinsCGG	p.Ser1661Arg	missense	N/A	ENSP00000507157.1	Q8IVF5-1
	TIAM2	ENST00000456877.6	TSL:1	c.2917_2919delAGTinsCGG	p.Ser973Arg	missense	N/A	ENSP00000407183.2	Q8IVF5-4
	TIAM2	ENST00000275246.11	TSL:1	c.1756_1758delAGTinsCGG	p.Ser586Arg	missense	N/A	ENSP00000275246.7	Q8IVF5-3

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr6-155578130;