chr17-76710936-G-A

Position:

• chr17-76710936-G-A

Variant summary

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

The NM_198530.4(MXRA7):​c.11C>T​(p.Pro4Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000589 in 849,250 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000059 (0 hom.)
• Consequence: MXRA7 NM_198530.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.60

Genes affected

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

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=0.17128783).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MXRA7	NM_198530.4	c.11C>T	p.Pro4Leu	missense_variant	1/4	ENST00000449428.7	NP_940932.2
MXRA7	NM_001008528.3	c.11C>T	p.Pro4Leu	missense_variant	1/4		NP_001008528.1
MXRA7	NM_001008529.3	c.11C>T	p.Pro4Leu	missense_variant	1/5		NP_001008529.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MXRA7	ENST00000449428.7	c.11C>T	p.Pro4Leu	missense_variant	1/4	1	NM_198530.4	ENSP00000391466	P2
MXRA7	ENST00000355797.7	c.11C>T	p.Pro4Leu	missense_variant	1/4	2		ENSP00000348050	A2
MXRA7	ENST00000375036.6	c.11C>T	p.Pro4Leu	missense_variant	1/5	2		ENSP00000364176	A2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000589 AC: 5 AN: 849250 Hom.: 0 Cov.: 29 AF XY: 0.00000757 AC XY: 3 AN XY: 396264

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: 0.00000258

Gnomad4 OTH exome AF: 0.000108

GnomAD4 genome Cov.: 30

Bravo AF: 0.00000378

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

Mar 21, 2022

The c.11C>T (p.P4L) alteration is located in exon 1 (coding exon 1) of the MXRA7 gene. This alteration results from a C to T substitution at nucleotide position 11, causing the proline (P) at amino acid position 4 to be replaced by a leucine (L). 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	Pathogenic	0.65
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	22
DANN	Benign	0.92
DEOGEN2	Benign	0.052	T;.;.
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.087	N
LIST_S2	Benign	0.35	T;T;T
M_CAP	Uncertain	0.092	D
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L;L;L
MutationTaster	Benign	0.93	N;N;N
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-1.9	N;D;D
REVEL	Benign	0.055
Sift	Pathogenic	0.0	D;D;D
Sift4G	Uncertain	0.012	D;D;D
Polyphen		0.83	P;P;P
Vest4		0.15
MutPred		0.32		Loss of loop (P = 0.0022);Loss of loop (P = 0.0022);Loss of loop (P = 0.0022);
MVP		0.12
MPC		0.10
ClinPred		0.27	T
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.16

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

LitVar

Other links and lift over

dbSNP: rs2076715789; hg19: chr17-74707018;