rs757488901

Variant names:

• chrX-3310380-G-A
• rs757488901
• NM_015419.4:c.7823C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-3310380-G-A
• chrX-3310380-G-C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_015419.4(MXRA5):​c.7823C>T​(p.Ser2608Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000015 in 1,203,782 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. S2608S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000092 (0 hom., 0 hem., cov: 19)
  • Exomes 𝑓: 0.000016 (0 hom. 5 hem.)
• Consequence: MXRA5 NM_015419.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.48
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13091564).
• BS2: High Hemizygotes in GnomAdExome4 at 5 gene

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.7823C>T	p.Ser2608Leu	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.7823C>T	p.Ser2608Leu	missense	Exon 7 of 7	ENSP00000217939.5	Q9NR99

Frequencies

GnomAD3 genomes AF: 0.00000923 AC: 1 AN: 108342 Hom.: 0 Cov.: 19

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000192

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000114 AC: 2 AN: 175031 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000739

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000155 AC: 17 AN: 1095440 Hom.: 0 Cov.: 35 AF XY: 0.0000138 AC XY: 5 AN XY: 361034

African (AFR) AF: 0.00 AC: 0 AN: 26316

American (AMR) AF: 0.0000570 AC: 2 AN: 35114

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19347

East Asian (EAS) AF: 0.00 AC: 0 AN: 30188

South Asian (SAS) AF: 0.00 AC: 0 AN: 54000

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40291

Middle Eastern (MID) AF: 0.000501 AC: 2 AN: 3994

European-Non Finnish (NFE) AF: 0.0000155 AC: 13 AN: 840248

Other (OTH) AF: 0.00 AC: 0 AN: 45942

GnomAD4 genome AF: 0.00000923 AC: 1 AN: 108342 Hom.: 0 Cov.: 19 AF XY: 0.00 AC XY: 0 AN XY: 30668

African (AFR) AF: 0.00 AC: 0 AN: 29858

American (AMR) AF: 0.00 AC: 0 AN: 10222

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2600

East Asian (EAS) AF: 0.00 AC: 0 AN: 3386

South Asian (SAS) AF: 0.00 AC: 0 AN: 2352

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5581

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 235

European-Non Finnish (NFE) AF: 0.0000192 AC: 1 AN: 51999

Other (OTH) AF: 0.00 AC: 0 AN: 1448

Alfa AF: 0.000102 Hom.: 1

Bravo AF: 0.00000756

ExAC AF: 0.0000248 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	16
DANN	Benign	0.90
DEOGEN2	Benign	0.0031	T
FATHMM_MKL	Benign	0.071	N
LIST_S2	Benign	0.82	T
M_CAP	Pathogenic	0.75	D
MetaRNN	Benign	0.13	T
MetaSVM	Uncertain	-0.13	T
MutationAssessor	Benign	-0.39	N
PhyloP100		3.5
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.39
Sift	Benign	0.33	T
Sift4G	Benign	0.31	T
Polyphen		0.42	B
Vest4		0.072
MutPred		0.53		Loss of disorder (P = 0.0306)
MVP		0.57
MPC		0.087
ClinPred		0.11	T
GERP RS		4.2
Varity_R		0.10
gMVP		0.44
Mutation Taster		=96/4	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: rs757488901; hg19: chrX-3228421; COSMIC: COSV108046074;