chr15-70892124-C-T

Variant names:

• chr15-70892124-C-T
• rs1397951830
• NM_020147.4:c.149G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020147.4(THAP10):​c.149G>A​(p.Arg50His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,530 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R50C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: THAP10 NM_020147.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.38
• Publications: 0 publications found

Genes affected

THAP10 (HGNC:23193): (THAP domain containing 10) This gene encodes a member of a family of proteins sharing an N-terminal Thanatos-associated domain. The Thanatos-associated domain contains a zinc finger signature similar to DNA-binding domains. This gene is part of a bidirectional gene pair on the long arm of chromosome 15 that is regulated by estrogen and may play a role in breast cancer. [provided by RefSeq, Nov 2010]

LRRC49 (HGNC:25965): (leucine rich repeat containing 49) Predicted to be involved in outer dynein arm assembly. Predicted to be located in microtubule. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25050873).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020147.4. 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
	THAP10	NM_020147.4	MANE Select	c.149G>A	p.Arg50His	missense	Exon 1 of 3	NP_064532.1	Q9P2Z0
	LRRC49	NM_001284357.2		c.19-1460C>T		intron	N/A	NP_001271286.1	Q8IUZ0-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THAP10	ENST00000249861.9	TSL:1 MANE Select	c.149G>A	p.Arg50His	missense	Exon 1 of 3	ENSP00000249861.4	Q9P2Z0
	LRRC49	ENST00000544974.6	TSL:2	c.19-1460C>T		intron	N/A	ENSP00000439600.2	Q8IUZ0-4
	THAP10	ENST00000560604.1	TSL:5	c.36+249G>A		intron	N/A	ENSP00000453920.1	H0YN95

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461530 Hom.: 0 Cov.: 65 AF XY: 0.00 AC XY: 0 AN XY: 727074

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86212

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53368

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111878

Other (OTH) AF: 0.00 AC: 0 AN: 60362

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.25	T
MetaSVM	Uncertain	0.13	D
MutationAssessor	Benign	-0.48	N
PhyloP100		1.4
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.020	N
REVEL	Benign	0.25
Sift	Benign	0.27	T
Sift4G	Uncertain	0.021	D
Polyphen		0.99	D
Vest4		0.22
MutPred		0.64		Loss of MoRF binding (P = 0.1317)
MVP		0.69
MPC		1.2
ClinPred		0.93	D
GERP RS		1.9
PromoterAI		-0.011	Neutral
Varity_R		0.056
gMVP		0.24
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: rs1397951830; hg19: chr15-71184463;