NM_032509.4:c.706-64G>C

Variant names:

• chr8-33498368-G-C
• rs2676419
• NM_032509.4:c.706-64G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.434
• Publications: 8 publications found

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

ACMG classification

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).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032509.4. 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
	MAK16	NM_032509.4	MANE Select	c.706-64G>C		intron	N/A	NP_115898.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAK16	ENST00000360128.11	TSL:1 MANE Select	c.706-64G>C		intron	N/A	ENSP00000353246.5
	MAK16	ENST00000518389.1	TSL:5	n.*246-64G>C		intron	N/A	ENSP00000430403.1
	TTI2	ENST00000519356.1	TSL:3	n.628+1960C>G		intron	N/A

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 v4.9

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

Other links and lift over

dbSNP: rs2676419; hg19: chr8-33355886;