X-3310282-T-C

Position:

• chrX-3310282-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015419.4(MXRA5):​c.7921A>G​(p.Lys2641Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000182 in 1,097,446 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 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 Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000018 (0 hom. 1 hem.)
• Consequence: MXRA5 NM_015419.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.73

Genes affected

MXRA5 (HGNC:7539): (matrix remodeling associated 5) This gene encodes one of the matrix-remodelling associated proteins. This protein contains 7 leucine-rich repeats and 12 immunoglobulin-like C2-type domains related to perlecan. This gene has a pseudogene on chromosome Y. [provided by RefSeq, Mar 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15288535).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MXRA5	NM_015419.4	c.7921A>G	p.Lys2641Glu	missense_variant	7/7	ENST00000217939.7	NP_056234.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MXRA5	ENST00000217939.7	c.7921A>G	p.Lys2641Glu	missense_variant	7/7	5	NM_015419.4	ENSP00000217939.5

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000182 AC: 2 AN: 1097446 Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 1 AN XY: 362816

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: 0.00000238

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

Dec 20, 2023

The c.7921A>G (p.K2641E) alteration is located in exon 7 (coding exon 6) of the MXRA5 gene. This alteration results from a A to G substitution at nucleotide position 7921, causing the lysine (K) at amino acid position 2641 to be replaced by a glutamic acid (E). 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	0.10
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	14
DANN	Benign	0.88
DEOGEN2	Benign	0.0015	T
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.50	N
REVEL	Benign	0.17
Sift	Benign	0.40	T
Sift4G	Uncertain	0.0070	D
Polyphen		0.67	P
Vest4		0.079
MutPred		0.40		Loss of ubiquitination at K2641 (P = 0.0199);
MVP		0.35
MPC		0.14
ClinPred		0.26	T
GERP RS		1.1
Varity_R		0.077
gMVP		0.43

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-3228323;