rs368680744

Variant names:

• chrX-126165295-G-A
• rs368680744
• NM_001013628.3:c.630C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-126165295-G-A
• chrX-126165295-G-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001013628.3(DCAF12L2):​c.630C>T​(p.Ser210Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000364 in 1,098,055 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. 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: 25)
  • Exomes 𝑓: 0.0000036 (0 hom. 0 hem.)
• Consequence: DCAF12L2 NM_001013628.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.273
• Publications: 0 publications found

Genes affected

DCAF12L2 (HGNC:32950): (DDB1 and CUL4 associated factor 12 like 2) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by Gly-His and Trp-Asp (GH-WD), which may facilitate formation of heterotrimeric or multi-protein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. This gene appears to represent an intronless retrocopy of a related multi-exon gene located on chromosome 9. However, the CDS of this intronless gene remains intact, it is conserved in other mammalian species, it is known to be transcribed, and it is therefore thought to encode a functional protein. [provided by RefSeq, May 2010]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP7: Synonymous conserved (PhyloP=0.273 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCAF12L2	NM_001013628.3	c.630C>T	p.Ser210Ser	synonymous_variant	Exon 1 of 1	ENST00000360028.4	NP_001013650.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCAF12L2	ENST00000360028.4	c.630C>T	p.Ser210Ser	synonymous_variant	Exon 1 of 1	6	NM_001013628.3	ENSP00000353128.2

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD2 exomes AF: 0.0000109 AC: 2 AN: 182841 AF XY: 0.00

Gnomad AFR exome AF: 0.000153

Gnomad AMR exome AF: 0.00

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: 0.00000364 AC: 4 AN: 1098055 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 363433

African (AFR) AF: 0.000152 AC: 4 AN: 26402

American (AMR) AF: 0.00 AC: 0 AN: 35205

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19386

East Asian (EAS) AF: 0.00 AC: 0 AN: 30206

South Asian (SAS) AF: 0.00 AC: 0 AN: 54143

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40422

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4107

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 842094

Other (OTH) AF: 0.00 AC: 0 AN: 46090

GnomAD4 genome Cov.: 25

Alfa AF: 0.0000508 Hom.: 1

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	2.6
DANN	Benign	0.62
PhyloP100		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs368680744; hg19: chrX-125299278;