rs769007634

Variant names:

• chrX-40630763-C-A
• rs769007634
• NM_144970.3:c.812G>T

Your query was ambiguous. Multiple possible variants found:

• chrX-40630763-C-A
• chrX-40630763-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_144970.3(CXorf38):​c.812G>T​(p.Arg271Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000913 in 1,095,564 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. 13/20 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. R271Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: CXorf38 NM_144970.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.646
• Publications: 0 publications found

Genes affected

CXorf38 (HGNC:28589): (chromosome X open reading frame 38)

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=0.13937661).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144970.3. 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
	CXorf38	NM_144970.3	MANE Select	c.812G>T	p.Arg271Leu	missense	Exon 6 of 7	NP_659407.1	Q8TB03-1
	CXorf38	NM_001330455.2		c.455G>T	p.Arg152Leu	missense	Exon 6 of 7	NP_001317384.1	Q8TB03-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXorf38	ENST00000327877.10	TSL:1 MANE Select	c.812G>T	p.Arg271Leu	missense	Exon 6 of 7	ENSP00000330488.5	Q8TB03-1
	CXorf38	ENST00000971744.1		c.929G>T	p.Arg310Leu	missense	Exon 7 of 8	ENSP00000641803.1
	CXorf38	ENST00000897030.1		c.812G>T	p.Arg271Leu	missense	Exon 6 of 7	ENSP00000567089.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.13e-7 AC: 1 AN: 1095564 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 361028

African (AFR) AF: 0.00 AC: 0 AN: 26321

American (AMR) AF: 0.00 AC: 0 AN: 34995

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19309

East Asian (EAS) AF: 0.00 AC: 0 AN: 30133

South Asian (SAS) AF: 0.00 AC: 0 AN: 53615

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4126

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 840652

Other (OTH) AF: 0.00 AC: 0 AN: 45993

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	5.0
DANN	Benign	0.93
DEOGEN2	Benign	0.019	T
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		-0.65
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.060
Sift	Benign	0.078	T
Sift4G	Benign	0.10	T
Polyphen		0.30	B
Vest4		0.27
MutPred		0.23		Gain of helix (P = 0.027)
MVP		0.32
MPC		0.67
ClinPred		0.29	T
GERP RS		-5.9
Varity_R		0.082
gMVP		0.22
Mutation Taster		=99/1	polymorphism

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: rs769007634; hg19: chrX-40490015;