chr4-82906512-C-G

Variant names:

• chr4-82906512-C-G
• rs139976656
• NM_024672.6:c.465C>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_024672.6(THAP9):​c.465C>G​(p.Ser155Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00546 in 1,613,706 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0044 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0056 (26 hom.)
• Consequence: THAP9 NM_024672.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.474
• Publications: 4 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]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 4-82906512-C-G is Benign according to our data. Variant chr4-82906512-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2654855.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.474 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

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.465C>G	p.Ser155Ser	synonymous	Exon 3 of 5	NP_078948.3
	THAP9	NM_001317776.2		c.33C>G	p.Ser11Ser	synonymous	Exon 4 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.465C>G	p.Ser155Ser	synonymous	Exon 3 of 5	ENSP00000305533.5	Q9H5L6
	THAP9	ENST00000505901.1	TSL:2	n.*222C>G		non_coding_transcript_exon	Exon 4 of 6	ENSP00000425966.1	F2Z371
	THAP9	ENST00000506208.1	TSL:3	n.87C>G		non_coding_transcript_exon	Exon 1 of 4	ENSP00000424001.1	H0Y9F3

Frequencies

GnomAD3 genomes AF: 0.00437 AC: 665 AN: 152010 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00118

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00629

Gnomad ASJ AF: 0.0251

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00123

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00595

Gnomad OTH AF: 0.00575

GnomAD2 exomes AF: 0.00498 AC: 1251 AN: 251278 AF XY: 0.00498

Gnomad AFR exome AF: 0.000985

Gnomad AMR exome AF: 0.00309

Gnomad ASJ exome AF: 0.0317

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00125

Gnomad NFE exome AF: 0.00628

Gnomad OTH exome AF: 0.00587

GnomAD4 exome AF: 0.00557 AC: 8148 AN: 1461578 Hom.: 26 Cov.: 31 AF XY: 0.00547 AC XY: 3979 AN XY: 727092

African (AFR) AF: 0.000598 AC: 20 AN: 33466

American (AMR) AF: 0.00333 AC: 149 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0288 AC: 753 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39654

South Asian (SAS) AF: 0.00148 AC: 128 AN: 86238

European-Finnish (FIN) AF: 0.00114 AC: 61 AN: 53418

Middle Eastern (MID) AF: 0.00625 AC: 36 AN: 5764

European-Non Finnish (NFE) AF: 0.00599 AC: 6662 AN: 1111818

Other (OTH) AF: 0.00561 AC: 339 AN: 60380

GnomAD4 genome AF: 0.00437 AC: 665 AN: 152128 Hom.: 5 Cov.: 32 AF XY: 0.00424 AC XY: 315 AN XY: 74370

African (AFR) AF: 0.00118 AC: 49 AN: 41526

American (AMR) AF: 0.00628 AC: 96 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0251 AC: 87 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4822

European-Finnish (FIN) AF: 0.00123 AC: 13 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00593 AC: 403 AN: 67930

Other (OTH) AF: 0.00569 AC: 12 AN: 2108

Alfa AF: 0.00490 Hom.: 1

Bravo AF: 0.00471

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00611

EpiControl AF: 0.00652

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	2.1
DANN	Benign	0.74
PhyloP100		-0.47
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs139976656; hg19: chr4-83827665; COSMIC: COSV56356958; COSMIC: COSV56356958;