GeneBe

8-33498368-G-C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032509.4(MAK16):​c.706-64G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

MAK16
NM_032509.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.434

Publications

8 publications found
Variant links:
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]
TTI2 Gene-Disease associations (from GenCC):
  • severe intellectual disability-short stature-behavioral abnormalities-facial dysmorphism syndrome
    Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, Orphanet

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAK16NM_032509.4 linkc.706-64G>C intron_variant Intron 9 of 9 ENST00000360128.11 NP_115898.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MAK16ENST00000360128.11 linkc.706-64G>C intron_variant Intron 9 of 9 1 NM_032509.4 ENSP00000353246.5
MAK16ENST00000518389.1 linkn.*246-64G>C intron_variant Intron 8 of 8 5 ENSP00000430403.1
TTI2ENST00000519356.1 linkn.628+1960C>G intron_variant Intron 5 of 5 3
TTI2ENST00000613904.1 linkc.*805C>G downstream_gene_variant 1 ENSP00000478396.1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
1293646
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
647506
African (AFR)
AF:
0.00
AC:
0
AN:
29716
American (AMR)
AF:
0.00
AC:
0
AN:
38268
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
22970
East Asian (EAS)
AF:
0.00
AC:
0
AN:
38254
South Asian (SAS)
AF:
0.00
AC:
0
AN:
77080
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
51180
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4998
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
976674
Other (OTH)
AF:
0.00
AC:
0
AN:
54506
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
CADD
Benign
0.45
DANN
Benign
0.14
PhyloP100
-0.43

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

Other links and lift over

dbSNP: rs2676419; hg19: chr8-33355886; API