rs8685

Positions:

• chr8-33500752-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000360128.11(MAK16):​c.*2123G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 410,674 control chromosomes in the GnomAD database, including 62,304 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.53 (21822 hom., cov: 32)
  • Exomes 𝑓: 0.56 (40482 hom.)
• Consequence: MAK16 ENST00000360128.11 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.34

Genes affected

MAK16 (HGNC:13703): (MAK16 homolog) Enables RNA binding activity. Predicted to be involved in maturation of 5.8S rRNA and maturation of LSU-rRNA. Located in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

TTI2 (HGNC:26262): (TELO2 interacting protein 2) This gene encodes a regulator of the DNA damage response. The protein is a component of the Triple T complex (TTT) which also includes telomere length regulation protein and TELO2 interacting protein 1. The TTT complex is involved in cellular resistance to DNA damage stresses and may act as a regulator of phosphoinositide-3-kinase-related protein kinase (PIKK) abundance. [provided by RefSeq, May 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAK16	NM_032509.4	c.*2123G>A		3_prime_UTR_variant	10/10	ENST00000360128.11	NP_115898.2
TTI2	NM_001102401.4	c.1260-262C>T		intron_variant		ENST00000431156.7	NP_001095871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAK16	ENST00000360128.11	c.*2123G>A		3_prime_UTR_variant	10/10	1	NM_032509.4	ENSP00000353246	P1
TTI2	ENST00000431156.7	c.1260-262C>T		intron_variant		1	NM_001102401.4	ENSP00000411169	P1

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80594 AN: 151780 Hom.: 21819 Cov.: 32

Gnomad AFR AF: 0.450

Gnomad AMI AF: 0.652

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.527

Gnomad EAS AF: 0.492

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.597

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.586

Gnomad OTH AF: 0.522

GnomAD4 exome AF: 0.557 AC: 144257 AN: 258778 Hom.: 40482 Cov.: 3 AF XY: 0.549 AC XY: 75947 AN XY: 138238

Gnomad4 AFR exome AF: 0.461

Gnomad4 AMR exome AF: 0.456

Gnomad4 ASJ exome AF: 0.529

Gnomad4 EAS exome AF: 0.512

Gnomad4 SAS exome AF: 0.447

Gnomad4 FIN exome AF: 0.605

Gnomad4 NFE exome AF: 0.594

Gnomad4 OTH exome AF: 0.572

GnomAD4 genome AF: 0.531 AC: 80623 AN: 151896 Hom.: 21822 Cov.: 32 AF XY: 0.530 AC XY: 39305 AN XY: 74224

Gnomad4 AFR AF: 0.449

Gnomad4 AMR AF: 0.495

Gnomad4 ASJ AF: 0.527

Gnomad4 EAS AF: 0.492

Gnomad4 SAS AF: 0.437

Gnomad4 FIN AF: 0.597

Gnomad4 NFE AF: 0.586

Gnomad4 OTH AF: 0.524

Alfa AF: 0.561 Hom.: 20216

Bravo AF: 0.521

Asia WGS AF: 0.439 AC: 1527 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.16
DANN	Benign	0.46

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: rs8685; hg19: chr8-33358270;