rs749140806

Variant names:

• chr15-70892188-C-G
• rs749140806
• NM_020147.4:c.85G>C

Your query was ambiguous. Multiple possible variants found:

• chr15-70892188-C-G
• chr15-70892188-C-T

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.85G>C​(p.Val29Leu) 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. 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. V29M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: THAP10 NM_020147.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.554
• Publications: 1 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=0.20987073).

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.85G>C	p.Val29Leu	missense	Exon 1 of 3	NP_064532.1	Q9P2Z0
	LRRC49	NM_001284357.2		c.19-1396C>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.85G>C	p.Val29Leu	missense	Exon 1 of 3	ENSP00000249861.4	Q9P2Z0
	LRRC49	ENST00000544974.6	TSL:2	c.19-1396C>G		intron	N/A	ENSP00000439600.2	Q8IUZ0-4
	THAP10	ENST00000560604.1	TSL:5	c.36+185G>C		intron	N/A	ENSP00000453920.1	H0YN95

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.040
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.068	N
LIST_S2	Benign	0.52	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.21	T
MetaSVM	Uncertain	0.068	D
MutationAssessor	Benign	-0.34	N
PhyloP100		0.55
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	0.17	N
REVEL	Uncertain	0.36
Sift	Benign	0.64	T
Sift4G	Benign	0.15	T
Polyphen		0.99	D
Vest4		0.27
MutPred		0.43		Loss of methylation at K25 (P = 0.0703)
MVP		0.46
MPC		0.73
ClinPred		0.85	D
GERP RS		2.5
PromoterAI		0.10	Neutral
Varity_R		0.085
gMVP		0.31

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: rs749140806; hg19: chr15-71184527;