chr4-82916975-T-C

Position:

• chr4-82916975-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 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: Not reported in ClinVar
• Conservation: PhyloP100: 4.04

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THAP9	NM_024672.6	c.763T>C	p.Phe255Leu	missense_variant	5/5	ENST00000302236.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THAP9	ENST00000302236.10	c.763T>C	p.Phe255Leu	missense_variant	5/5	1	NM_024672.6	P1
THAP9	ENST00000505901.1	c.*520T>C		3_prime_UTR_variant, NMD_transcript_variant	6/6	2
THAP9	ENST00000506208.1	c.*134T>C		3_prime_UTR_variant, NMD_transcript_variant	4/4	3
LIN54	ENST00000505905.1	n.305-3534A>G		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR exome AF: 0.0000645

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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
MutationTaster	Benign	0.68	N;N
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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1721051124; hg19: chr4-83838128;