rs10568542

Variant names:

• chr6-155257579-AAGAT-A
• rs10568542
• NM_012454.4:c.*463_*466delAGAT

Your query was ambiguous. Multiple possible variants found:

• chr6-155257579-AAGAT-A
• chr6-155257579-AAGAT-AAGATAGAT

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.48
• Publications: 6 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: 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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIAM2	NM_012454.4	MANE Select	c.*463_*466delAGAT		3_prime_UTR	Exon 27 of 27	NP_036586.3
	TFB1M	NM_016020.4	MANE Select	c.*253_*256delATCT		3_prime_UTR	Exon 7 of 7	NP_057104.2
	TIAM2	NM_001384546.1		c.*463_*466delAGAT		3_prime_UTR	Exon 27 of 27	NP_001371475.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIAM2	ENST00000682666.1	MANE Select	c.*463_*466delAGAT		3_prime_UTR	Exon 27 of 27	ENSP00000507157.1
	TFB1M	ENST00000367166.5	TSL:1 MANE Select	c.*253_*256delATCT		3_prime_UTR	Exon 7 of 7	ENSP00000356134.4
	TIAM2	ENST00000360366.8	TSL:5	c.*463_*466delAGAT		3_prime_UTR	Exon 25 of 25	ENSP00000353528.4

Frequencies

GnomAD3 genomes AF: 0.742 AC: 112535 AN: 151636 Hom.: 42409 Cov.: 0

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

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

GnomAD4 genome AF: 0.742 AC: 112667 AN: 151754 Hom.: 42477 Cov.: 0 AF XY: 0.743 AC XY: 55112 AN XY: 74152

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.5
Mutation Taster		=100/0	polymorphism (auto)

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: rs10568542; hg19: chr6-155578713; COSMIC: COSV51637306; COSMIC: COSV51637306;