rs544136510

Variant names:

• chr15-70882775-C-A
• rs544136510
• NM_020147.4:c.563G>T

Your query was ambiguous. Multiple possible variants found:

• chr15-70882775-C-A
• chr15-70882775-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020147.4(THAP10):​c.563G>T​(p.Arg188Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict 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. R188C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: THAP10 NM_020147.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.152
• 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: 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 (MetaRNN=0.03158644).

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.563G>T	p.Arg188Leu	missense	Exon 2 of 3	NP_064532.1	Q9P2Z0
	LRRC49	NM_001284357.2		c.18+9552C>A		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.563G>T	p.Arg188Leu	missense	Exon 2 of 3	ENSP00000249861.4	Q9P2Z0
	THAP10	ENST00000560604.1	TSL:5	c.170G>T	p.Arg57Leu	missense	Exon 2 of 3	ENSP00000453920.1	H0YN95
	LRRC49	ENST00000544974.6	TSL:2	c.18+9552C>A		intron	N/A	ENSP00000439600.2	Q8IUZ0-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461828 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727212

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000671 AC: 3 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

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

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111982

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	5.6
DANN	Benign	0.80
DEOGEN2	Benign	0.021	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0069	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.15
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.25	N
REVEL	Benign	0.022
Sift	Benign	0.22	T
Sift4G	Benign	0.20	T
Polyphen		0.0	B
Vest4		0.11
MutPred		0.28		Loss of solvent accessibility (P = 0.0079)
MVP		0.014
MPC		0.41
ClinPred		0.042	T
GERP RS		-0.081
Varity_R		0.079
gMVP		0.061
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: rs544136510; hg19: chr15-71175114;