6-125229180-G-A

Variant names:

• chr6-125229180-G-A
• rs760514773
• NM_003287.4:c.198G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_003287.4(TPD52L1):​c.198G>A​(p.Glu66Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,308 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.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TPD52L1 NM_003287.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.700
• Publications: 0 publications found

Genes affected

TPD52L1 (HGNC:12006): (TPD52 like 1) This gene encodes a member of a family of proteins that contain coiled-coil domains and may form hetero- or homomers. The encoded protein is involved in cell proliferation and calcium signaling. It also interacts with the mitogen-activated protein kinase kinase kinase 5 (MAP3K5/ASK1) and positively regulates MAP3K5-induced apoptosis. Multiple alternatively spliced transcript variants have been observed. [provided by RefSeq, Jan 2016]

HDDC2 (HGNC:21078): (HD domain containing 2) Predicted to enable 5'-deoxynucleotidase activity. Predicted to be involved in dephosphorylation. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP7: Synonymous conserved (PhyloP=0.7 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003287.4. 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
	TPD52L1	NM_003287.4	MANE Select	c.198G>A	p.Glu66Glu	synonymous	Exon 3 of 7	NP_003278.1	Q16890-1
	TPD52L1	NM_001318903.2		c.198G>A	p.Glu66Glu	synonymous	Exon 3 of 8	NP_001305832.1	J3KNE7
	TPD52L1	NM_001300994.3		c.198G>A	p.Glu66Glu	synonymous	Exon 3 of 6	NP_001287923.1	E9PPQ1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPD52L1	ENST00000534000.6	TSL:1 MANE Select	c.198G>A	p.Glu66Glu	synonymous	Exon 3 of 7	ENSP00000434142.1	Q16890-1
	TPD52L1	ENST00000368402.9	TSL:1	c.198G>A	p.Glu66Glu	synonymous	Exon 3 of 6	ENSP00000357387.5	Q16890-2
	TPD52L1	ENST00000368388.6	TSL:1	c.198G>A	p.Glu66Glu	synonymous	Exon 3 of 5	ENSP00000357373.2	Q16890-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461308 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726932

African (AFR) AF: 0.00 AC: 0 AN: 33434

American (AMR) AF: 0.00 AC: 0 AN: 44644

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39642

South Asian (SAS) AF: 0.00 AC: 0 AN: 86190

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111774

Other (OTH) AF: 0.00 AC: 0 AN: 60360

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	8.4
DANN	Benign	0.62
PhyloP100		0.70

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: rs760514773; hg19: chr6-125550326;