15-70882564-G-A

Variant names:

• chr15-70882564-G-A
• rs746416963
• NM_020147.4:c.664C>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.664C>T​(p.Leu222Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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. L222V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: THAP10 NM_020147.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.200
• 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=0.06796661).

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.664C>T	p.Leu222Phe	missense	Exon 3 of 3	NP_064532.1	Q9P2Z0
	LRRC49	NM_001284357.2		c.18+9341G>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.664C>T	p.Leu222Phe	missense	Exon 3 of 3	ENSP00000249861.4	Q9P2Z0
	THAP10	ENST00000560604.1	TSL:5	c.271C>T	p.Leu91Phe	missense	Exon 3 of 3	ENSP00000453920.1	H0YN95
	LRRC49	ENST00000544974.6	TSL:2	c.18+9341G>A		intron	N/A	ENSP00000439600.2	Q8IUZ0-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.037	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.068	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.20
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.53	N
REVEL	Benign	0.050
Sift	Uncertain	0.014	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.94	P
Vest4		0.069
MutPred		0.21		Gain of helix (P = 0.0117)
MVP		0.030
MPC		0.65
ClinPred		0.12	T
GERP RS		0.21
Varity_R		0.12
gMVP		0.043

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs746416963; hg19: chr15-71174903;