X-71106087-T-C

Position:

• chrX-71106087-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001025265.3(CXorf65):​c.163A>G​(p.Met55Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,097,252 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. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: CXorf65 NM_001025265.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.711

Genes affected

CXorf65 (HGNC:33713): (chromosome X open reading frame 65)

ENSG00000285171 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.048981726).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CXorf65	NM_001025265.3	c.163A>G	p.Met55Val	missense_variant	3/6	ENST00000374251.6	NP_001020436.1
CXorf65	XM_005262244.5	c.163A>G	p.Met55Val	missense_variant	3/5		XP_005262301.1
CXorf65	NR_033212.2	n.328A>G		non_coding_transcript_exon_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CXorf65	ENST00000374251.6	c.163A>G	p.Met55Val	missense_variant	3/6	5	NM_001025265.3	ENSP00000363369.4
ENSG00000285171	ENST00000646505.1	n.*471A>G		non_coding_transcript_exon_variant	9/12			ENSP00000496673.1
ENSG00000285171	ENST00000646505.1	n.*471A>G		3_prime_UTR_variant	9/12			ENSP00000496673.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1097252 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 362612

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000119

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 21, 2021

The c.163A>G (p.M55V) alteration is located in exon 3 (coding exon 3) of the CXorf65 gene. This alteration results from a A to G substitution at nucleotide position 163, causing the methionine (M) at amino acid position 55 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.0020
DANN	Benign	0.45
DEOGEN2	Benign	0.0076	T
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PROVEAN	Benign	-0.55	N
REVEL	Benign	0.034
Sift	Benign	0.53	T
Sift4G	Benign	1.0	T
Polyphen		0.025	B
Vest4		0.13
MutPred		0.32		Gain of sheet (P = 0.0101);
MVP		0.34
MPC		0.17
ClinPred		0.017	T
GERP RS		-6.5
Varity_R		0.054
gMVP		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-70325937;