8-33498368-G-T

Position:

• chr8-33498368-G-T

Variant summary

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

The NM_032509.4(MAK16):​c.706-64G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 1,442,360 control chromosomes in the GnomAD database, including 285,331 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 0.64 (31002 hom., cov: 31)
  • Exomes 𝑓: 0.62 (254329 hom.)
• Consequence: MAK16 NM_032509.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.434

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAK16	NM_032509.4	c.706-64G>T		intron_variant		ENST00000360128.11	NP_115898.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAK16	ENST00000360128.11	c.706-64G>T		intron_variant		1	NM_032509.4	ENSP00000353246.5
MAK16	ENST00000518389.1	n.*246-64G>T		intron_variant		5		ENSP00000430403.1
TTI2	ENST00000519356.1	n.628+1960C>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.636 AC: 96458 AN: 151606 Hom.: 30985 Cov.: 31

Gnomad AFR AF: 0.682

Gnomad AMI AF: 0.666

Gnomad AMR AF: 0.551

Gnomad ASJ AF: 0.591

Gnomad EAS AF: 0.571

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.651

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.643

Gnomad OTH AF: 0.618

GnomAD4 exome AF: 0.625 AC: 806550 AN: 1290640 Hom.: 254329 AF XY: 0.622 AC XY: 401574 AN XY: 646002

Gnomad4 AFR exome AF: 0.684

Gnomad4 AMR exome AF: 0.445

Gnomad4 ASJ exome AF: 0.590

Gnomad4 EAS exome AF: 0.566

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.649

Gnomad4 NFE exome AF: 0.642

Gnomad4 OTH exome AF: 0.631

GnomAD4 genome AF: 0.636 AC: 96515 AN: 151720 Hom.: 31002 Cov.: 31 AF XY: 0.634 AC XY: 47021 AN XY: 74144

Gnomad4 AFR AF: 0.681

Gnomad4 AMR AF: 0.550

Gnomad4 ASJ AF: 0.591

Gnomad4 EAS AF: 0.571

Gnomad4 SAS AF: 0.497

Gnomad4 FIN AF: 0.651

Gnomad4 NFE AF: 0.643

Gnomad4 OTH AF: 0.621

Alfa AF: 0.585 Hom.: 3185

Bravo AF: 0.631

Asia WGS AF: 0.524 AC: 1824 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.43
DANN	Benign	0.53

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: rs2676419; hg19: chr8-33355886;