17-76688114-G-C

Variant names:

• chr17-76688114-G-C
• NM_198530.4:c.405C>G
• MXRA7 p.Asp135Glu

Variant summary

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

The NM_198530.4(MXRA7):​c.405C>G​(p.Asp135Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 18/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MXRA7 NM_198530.4 missense, splice_region
• Scores: Splicing: ADA: 0.0004715
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.83
• Publications: 0 publications found

Genes affected

MXRA7 (HGNC:7541): (matrix remodeling associated 7) Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

SNHG16 (HGNC:44352): (small nucleolar RNA host gene 16)

ENSG00000296346 (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=0.066352576).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198530.4. 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
	MXRA7	NM_198530.4	MANE Select	c.405C>G	p.Asp135Glu	missense splice_region	Exon 2 of 4	NP_940932.2
	MXRA7	NM_001387276.1		c.534C>G	p.Asp178Glu	missense splice_region	Exon 1 of 3	NP_001374205.1
	MXRA7	NM_001387277.1		c.534C>G	p.Asp178Glu	missense splice_region	Exon 1 of 4	NP_001374206.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MXRA7	ENST00000449428.7	TSL:1 MANE Select	c.405C>G	p.Asp135Glu	missense splice_region	Exon 2 of 4	ENSP00000391466.1	P84157-2
	MXRA7	ENST00000592148.1	TSL:1	c.534C>G	p.Asp178Glu	missense splice_region	Exon 1 of 3	ENSP00000465103.1	Q6ZR64
	MXRA7	ENST00000355797.7	TSL:2	c.405C>G	p.Asp135Glu	missense splice_region	Exon 2 of 4	ENSP00000348050.2	P84157-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	0.24
DANN	Benign	0.34
DEOGEN2	Benign	0.0068	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.068	D
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		-1.8
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.11
Sift	Benign	0.33	T
Sift4G	Benign	0.26	T
Varity_R		0.057
gMVP		0.0036

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00047
dbscSNV1_RF	Benign	0.020
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr17-74684196;