15-70882769-C-G

Variant names:

• chr15-70882769-C-G
• rs144217156
• NM_020147.4:c.569G>C

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.569G>C​(p.Arg190Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,614,114 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. R190H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: THAP10 NM_020147.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.906
• 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=0.05879894).

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.569G>C	p.Arg190Pro	missense	Exon 2 of 3	NP_064532.1	Q9P2Z0
	LRRC49	NM_001284357.2		c.18+9546C>G		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.569G>C	p.Arg190Pro	missense	Exon 2 of 3	ENSP00000249861.4	Q9P2Z0
	THAP10	ENST00000560604.1	TSL:5	c.176G>C	p.Arg59Pro	missense	Exon 2 of 3	ENSP00000453920.1	H0YN95
	LRRC49	ENST00000544974.6	TSL:2	c.18+9546C>G		intron	N/A	ENSP00000439600.2	Q8IUZ0-4

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152182 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251220 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461814 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727206

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

American (AMR) AF: 0.0000224 AC: 1 AN: 44716

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: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111978

Other (OTH) AF: 0.0000166 AC: 1 AN: 60392

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152300 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74468

African (AFR) AF: 0.00 AC: 0 AN: 41578

American (AMR) AF: 0.0000654 AC: 1 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2114

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	14
DANN	Benign	0.96
DEOGEN2	Benign	0.058	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L
PhyloP100		-0.91
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.087
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.50	P
Vest4		0.23
MutPred		0.37		Gain of sheet (P = 0.0101)
MVP		0.014
MPC		0.96
ClinPred		0.42	T
GERP RS		-2.5
Varity_R		0.38
gMVP		0.35

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: rs144217156; hg19: chr15-71175108;