chr1-1354089-G-C

Variant names:

• chr1-1354089-G-C
• rs1423681920
• NM_032348.4:c.1163C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032348.4(MXRA8):​c.1163C>G​(p.Ala388Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,640 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 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. A388V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MXRA8 NM_032348.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.989
• Publications: 0 publications found

Genes affected

MXRA8 (HGNC:7542): (matrix remodeling associated 8) Predicted to be involved in establishment of glial blood-brain barrier. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000304860 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.043351173).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032348.4. 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
	MXRA8	NM_032348.4	MANE Select	c.1163C>G	p.Ala388Gly	missense	Exon 8 of 10	NP_115724.1	Q9BRK3-1
	MXRA8	NM_001282585.1		c.1163C>G	p.Ala388Gly	missense	Exon 8 of 10	NP_001269514.1	Q9BRK3-2
	MXRA8	NM_001282582.2		c.1163C>G	p.Ala388Gly	missense	Exon 9 of 11	NP_001269511.1	Q9BRK3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MXRA8	ENST00000309212.11	TSL:1 MANE Select	c.1163C>G	p.Ala388Gly	missense	Exon 8 of 10	ENSP00000307887.6	Q9BRK3-1
	MXRA8	ENST00000342753.8	TSL:1	c.860C>G	p.Ala287Gly	missense	Exon 7 of 9	ENSP00000344998.4	Q9BRK3-4
	MXRA8	ENST00000474033.5	TSL:1	n.90C>G		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460640 Hom.: 0 Cov.: 76 AF XY: 0.00000138 AC XY: 1 AN XY: 726596

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52244

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111964

Other (OTH) AF: 0.00 AC: 0 AN: 60374

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	2.6
DANN	Benign	0.47
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.097	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.99
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.85	N
REVEL	Benign	0.030
Sift	Benign	0.34	T
Sift4G	Benign	0.39	T
Polyphen		0.0	B
Vest4		0.18
MutPred		0.20		Gain of sheet (P = 0.0344)
MVP		0.030
MPC		0.14
ClinPred		0.085	T
GERP RS		-8.2
Varity_R		0.055
gMVP		0.19
Mutation Taster		=87/13	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: rs1423681920; hg19: chr1-1289469;