rs10568542

chr6-155257579-AAGAT-Achr6-155257579-AAGAT-AAGATAGAT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_012454.4(TIAM2):c.*463_*466del 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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
TIAM2	NM_012454.4	c.*463_*466del		3_prime_UTR_variant	27/27	ENST00000682666.1
TFB1M	NM_016020.4	c.*253_*256del		3_prime_UTR_variant	7/7	ENST00000367166.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TFB1M	ENST00000367166.5	c.*253_*256del		3_prime_UTR_variant	7/7	1	NM_016020.4	P1
TIAM2	ENST00000682666.1	c.*463_*466del		3_prime_UTR_variant	27/27		NM_012454.4	A2
TIAM2	ENST00000360366.8	c.*463_*466del		3_prime_UTR_variant	25/25	5		A2
TIAM2	ENST00000461783.7	c.*463_*466del		3_prime_UTR_variant	29/29	2		A2

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

Gnomad4 AFR exome AF: 0.845

Gnomad4 AMR exome AF: 0.782

Gnomad4 ASJ exome AF: 0.580

Gnomad4 EAS exome AF: 0.987

Gnomad4 SAS exome AF: 0.730

Gnomad4 FIN exome AF: 0.673

Gnomad4 NFE exome AF: 0.674

Gnomad4 OTH exome AF: 0.700

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

Gnomad4 AFR AF: 0.847

Gnomad4 AMR AF: 0.756

Gnomad4 ASJ AF: 0.583

Gnomad4 EAS AF: 0.988

Gnomad4 SAS AF: 0.752

Gnomad4 FIN AF: 0.675

Gnomad4 NFE AF: 0.678

Gnomad4 OTH AF: 0.710

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

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

Other links and lift over

dbSNP: rs10568542; hg19: chr6-155578713;