chr4-82916975-T-C

Variant names:

• chr4-82916975-T-C
• rs1721051124
• NM_024672.6:c.763T>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024672.6(THAP9):​c.763T>C​(p.Phe255Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000144 in 1,389,218 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: THAP9 NM_024672.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.04
• Publications: 0 publications found

Genes affected

THAP9 (HGNC:23192): (THAP domain containing 9) Enables sequence-specific DNA binding activity and transposase activity. Involved in DNA integration and transposition, DNA-mediated. [provided by Alliance of Genome Resources, Apr 2022]

LIN54 (HGNC:25397): (lin-54 DREAM MuvB core complex component) LIN54 is a component of the LIN, or DREAM, complex, an essential regulator of cell cycle genes (Schmit et al., 2009 [PubMed 19725879]).[supplied by OMIM, Dec 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40224248).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024672.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THAP9	NM_024672.6	MANE Select	c.763T>C	p.Phe255Leu	missense	Exon 5 of 5	NP_078948.3
	THAP9	NM_001317776.2		c.331T>C	p.Phe111Leu	missense	Exon 6 of 6	NP_001304705.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THAP9	ENST00000302236.10	TSL:1 MANE Select	c.763T>C	p.Phe255Leu	missense	Exon 5 of 5	ENSP00000305533.5	Q9H5L6
	THAP9	ENST00000505901.1	TSL:2	n.*520T>C		non_coding_transcript_exon	Exon 6 of 6	ENSP00000425966.1	F2Z371
	THAP9	ENST00000506208.1	TSL:3	n.*134T>C		non_coding_transcript_exon	Exon 4 of 4	ENSP00000424001.1	H0Y9F3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000144 AC: 2 AN: 1389218 Hom.: 0 Cov.: 30 AF XY: 0.00000146 AC XY: 1 AN XY: 683858

African (AFR) AF: 0.0000645 AC: 2 AN: 31022

American (AMR) AF: 0.00 AC: 0 AN: 32588

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21572

East Asian (EAS) AF: 0.00 AC: 0 AN: 39132

South Asian (SAS) AF: 0.00 AC: 0 AN: 73174

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50786

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5426

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078252

Other (OTH) AF: 0.00 AC: 0 AN: 57266

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Benign	-0.026	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.026	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		4.0
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.23
Sift	Uncertain	0.0080	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.36
MutPred		0.33		Loss of glycosylation at P253 (P = 0.0645)
MVP		0.39
MPC		0.36
ClinPred		0.86	D
GERP RS		3.8
Varity_R		0.59
gMVP		0.51
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1721051124; hg19: chr4-83838128;