Genetic Variant NM_012454.4:c.*463_*466delAGAT (chr6-155257579-AAGAT-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_012454.4(TIAM2):c.*463_*466delAGAT variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.718 in 445,690 control chromosomes in the GnomAD database, including 117,016 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.74 ( 42477 hom., cov: 0)

Exomes 𝑓: 0.71 ( 74539 hom. )

Consequence

TIAM2
NM_012454.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.48

Publications

6 publications found

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]

TIAM2 links:

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]

TFB1M links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.965 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TIAM2	NM_012454.4 link	c.463_466delAGAT		3_prime_UTR_variant	Exon 27 of 27	ENST00000682666.1	NP_036586.3	Q8IVF5-1B3KW11
TFB1M	NM_016020.4 link	c.253_256delATCT		3_prime_UTR_variant	Exon 7 of 7	ENST00000367166.5	NP_057104.2	Q8WVM0E5KTM5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TIAM2	ENST00000682666.1 link	c.463_466delAGAT		3_prime_UTR_variant	Exon 27 of 27		NM_012454.4	ENSP00000507157.1		Q8IVF5-1
TFB1M	ENST00000367166.5 link	c.253_256delATCT		3_prime_UTR_variant	Exon 7 of 7	1	NM_016020.4	ENSP00000356134.4		Q8WVM0

Frequencies

GnomAD3 genomes

AF:

0.742

AC:

112535

AN:

151636

Hom.:

42409

Cov.:

show subpopulations

Gnomad AFR

AF:

0.847

Gnomad AMI

AF:

0.636

Gnomad AMR

AF:

0.756

Gnomad ASJ

AF:

0.583

Gnomad EAS

AF:

0.988

Gnomad SAS

AF:

0.752

Gnomad FIN

AF:

0.675

Gnomad MID

AF:

0.571

Gnomad NFE

AF:

0.678

Gnomad OTH

AF:

0.707

GnomAD4 exome

AF:

0.705

AC:

207296

AN:

293936

Hom.:

74539

AF XY:

0.706

AC XY:

109442

AN XY:

155108

show subpopulations

African (AFR)

AF:

0.845

AC:

7305

AN:

8650

American (AMR)

AF:

0.782

AC:

7067

AN:

9042

Ashkenazi Jewish (ASJ)

AF:

0.580

AC:

5450

AN:

9396

East Asian (EAS)

AF:

0.987

AC:

17968

AN:

18210

South Asian (SAS)

AF:

0.730

AC:

20446

AN:

28014

European-Finnish (FIN)

AF:

0.673

AC:

10383

AN:

15424

Middle Eastern (MID)

AF:

0.600

AC:

842

AN:

1404

European-Non Finnish (NFE)

AF:

0.674

AC:

125789

AN:

186590

Other (OTH)

AF:

0.700

AC:

12046

AN:

17206

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

2854

5708

8561

11415

14269

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.742

AC:

112667

AN:

151754

Hom.:

42477

Cov.:

AF XY:

0.743

AC XY:

55112

AN XY:

74152

show subpopulations

African (AFR)

AF:

0.847

AC:

35055

AN:

41380

American (AMR)

AF:

0.756

AC:

11523

AN:

15242

Ashkenazi Jewish (ASJ)

AF:

0.583

AC:

2021

AN:

3466

East Asian (EAS)

AF:

0.988

AC:

5102

AN:

5166

South Asian (SAS)

AF:

0.752

AC:

3626

AN:

4820

European-Finnish (FIN)

AF:

0.675

AC:

7084

AN:

10500

Middle Eastern (MID)

AF:

0.569

AC:

164

AN:

288

European-Non Finnish (NFE)

AF:

0.678

AC:

46024

AN:

67884

Other (OTH)

AF:

0.710

AC:

1492

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1394

2788

4181

5575

6969

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.605

Hom.:

1599

Bravo

AF:

0.756

Asia WGS

AF:

0.882

AC:

3062

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

4.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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NM_012454.4:c.463_466delAGAT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over