X-40630763-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_144970.3(CXorf38):​c.812G>A​(p.Arg271Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000183 in 1,095,571 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.000018 (0 hom. 4 hem.)
• Consequence: CXorf38 NM_144970.3 missense
• Clinical Significance: Likely benign no assertion criteria provided B:2
• Conservation: PhyloP100: -0.646
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.047884315).
• BP6: Variant X-40630763-C-T is Benign according to our data. Variant chrX-40630763-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1206123.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Hemizygotes in GnomAdExome4 at 4 gene

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>A	p.Arg271Gln	missense	Exon 6 of 7	NP_659407.1	Q8TB03-1
	CXorf38	NM_001330455.2		c.455G>A	p.Arg152Gln	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>A	p.Arg271Gln	missense	Exon 6 of 7	ENSP00000330488.5	Q8TB03-1
	CXorf38	ENST00000971744.1		c.929G>A	p.Arg310Gln	missense	Exon 7 of 8	ENSP00000641803.1
	CXorf38	ENST00000897030.1		c.812G>A	p.Arg271Gln	missense	Exon 6 of 7	ENSP00000567089.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.0000111 AC: 2 AN: 179942 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000738

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000124

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000183 AC: 20 AN: 1095571 Hom.: 0 Cov.: 28 AF XY: 0.0000111 AC XY: 4 AN XY: 361031

African (AFR) AF: 0.0000380 AC: 1 AN: 26321

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19310

East Asian (EAS) AF: 0.0000332 AC: 1 AN: 30133

South Asian (SAS) AF: 0.0000186 AC: 1 AN: 53621

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: 0.0000131 AC: 11 AN: 840652

Other (OTH) AF: 0.000130 AC: 6 AN: 45993

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.41
DANN	Benign	0.51
DEOGEN2	Benign	0.0070	T
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.48	N
PhyloP100		-0.65
PROVEAN	Benign	-0.81	N
REVEL	Benign	0.070
Sift	Benign	0.60	T
Sift4G	Benign	0.80	T
Polyphen		0.0050	B
Vest4		0.072
MutPred		0.13		Gain of methylation at K276 (P = 0.103)
MVP		0.13
MPC		0.51
ClinPred		0.016	T
GERP RS		-5.9
Varity_R		0.033
gMVP		0.048
Mutation Taster		=97/3	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;