X-154401914-C-T

Variant names:

• chrX-154401914-C-T
• rs12877
• NM_001303620.2:c.*793G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001303620.2(DNASE1L1):​c.*793G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000036 in 111,155 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: 𝑓 0.000036 (0 hom., 0 hem., cov: 23)
• Consequence: DNASE1L1 NM_001303620.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.76
• Publications: 2 publications found

Genes affected

DNASE1L1 (HGNC:2957): (deoxyribonuclease 1 like 1) This gene encodes a deoxyribonuclease protein that shows high sequence similarity to DNase I. The encoded protein is localized to the endoplasmic reticulum and modified by N-linked glycosylation. Alternate transcriptional splice variants encoding the same protein have been observed. [provided by RefSeq, Jan 2015]

RPL10 (HGNC:10298): (ribosomal protein L10) This gene encodes a ribosomal protein that is a component of the 60S ribosome subunit. The related protein in chicken can bind to c-Jun and can repress c-Jun-mediated transcriptional activation. Some studies have detected an association between variation in this gene and autism spectrum disorders, though others do not detect this relationship. There are multiple pseudogenes of this gene dispersed throughout the genome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

RPL10 Gene-Disease associations (from GenCC):

• intellectual disability, X-linked, syndromic, 35

  Inheritance: XL Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• X-linked syndromic intellectual disability

  Inheritance: XL Classification: MODERATE Submitted by: ClinGen
• X-linked intellectual disability-cerebellar hypoplasia-spondylo-epiphyseal dysplasia syndrome

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
• X-linked microcephaly-growth retardation-prognathism-cryptorchidism syndrome

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
• autism, susceptibility to, X-linked 5

  Inheritance: Unknown, XL Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

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 (Cadd=0.492).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNASE1L1	NM_001303620.2	c.*793G>A		3_prime_UTR_variant	Exon 8 of 8	ENST00000369807.6	NP_001290549.1
RPL10	NM_006013.5	c.*1060C>T		3_prime_UTR_variant	Exon 7 of 7	ENST00000369817.7	NP_006004.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNASE1L1	ENST00000369807.6	c.*793G>A		3_prime_UTR_variant	Exon 8 of 8	1	NM_001303620.2	ENSP00000358822.1
RPL10	ENST00000369817.7	c.*1060C>T		3_prime_UTR_variant	Exon 7 of 7	5	NM_006013.5	ENSP00000358832.2

Frequencies

GnomAD3 genomes AF: 0.0000360 AC: 4 AN: 111155 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.000132

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.0000360 AC: 4 AN: 111155 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 33385

African (AFR) AF: 0.000132 AC: 4 AN: 30329

American (AMR) AF: 0.00 AC: 0 AN: 10497

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2649

East Asian (EAS) AF: 0.00 AC: 0 AN: 3582

South Asian (SAS) AF: 0.00 AC: 0 AN: 2675

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6007

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 234

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53009

Other (OTH) AF: 0.00 AC: 0 AN: 1489

Alfa AF: 0.00 Hom.: 297

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
CADD	Benign	0.49
PhyloP100		-1.8

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: rs12877; hg19: -;