rs1242878395

Variant names:

• chrX-3310339-C-A
• rs1242878395
• NM_015419.4:c.7864G>T

Your query was ambiguous. Multiple possible variants found:

• chrX-3310339-C-A
• chrX-3310339-C-T

Variant summary

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

The NM_015419.4(MXRA5):​c.7864G>T​(p.Ala2622Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000918 in 1,089,823 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. 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. A2622T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 21)
  • Exomes 𝑓: 9.2e-7 (0 hom. 0 hem.)
• Consequence: MXRA5 NM_015419.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.42
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015419.4. 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
	MXRA5	NM_015419.4	MANE Select	c.7864G>T	p.Ala2622Ser	missense	Exon 7 of 7	NP_056234.2	Q9NR99

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MXRA5	ENST00000217939.7	TSL:5 MANE Select	c.7864G>T	p.Ala2622Ser	missense	Exon 7 of 7	ENSP00000217939.5	Q9NR99

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD2 exomes AF: 0.00000555 AC: 1 AN: 180209 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: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000125

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 9.18e-7 AC: 1 AN: 1089823 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 355591

African (AFR) AF: 0.00 AC: 0 AN: 26139

American (AMR) AF: 0.00 AC: 0 AN: 35124

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19318

East Asian (EAS) AF: 0.00 AC: 0 AN: 30206

South Asian (SAS) AF: 0.00 AC: 0 AN: 53952

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40302

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4013

European-Non Finnish (NFE) AF: 0.00000120 AC: 1 AN: 834943

Other (OTH) AF: 0.00 AC: 0 AN: 45826

GnomAD4 genome Cov.: 21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0067	T
FATHMM_MKL	Benign	0.30	N
LIST_S2	Uncertain	0.87	D
M_CAP	Pathogenic	0.59	D
MetaRNN	Uncertain	0.59	D
MetaSVM	Benign	-0.51	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		2.4
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.35
Sift	Benign	0.062	T
Sift4G	Uncertain	0.010	D
Polyphen		1.0	D
Vest4		0.11
MutPred		0.65		Gain of disorder (P = 0.0351)
MVP		0.35
MPC		0.37
ClinPred		0.50	D
GERP RS		4.2
Varity_R		0.18
gMVP		0.51
Mutation Taster		=98/2	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: rs1242878395; hg19: chrX-3228380; COSMIC: COSV54229495;