chr17-76710628-C-T

Variant names:

• chr17-76710628-C-T
• rs762048171
• NM_198530.4:c.319G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198530.4(MXRA7):​c.319G>A​(p.Glu107Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000506 in 1,383,644 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0000049 (0 hom.)
• Consequence: MXRA7 NM_198530.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0110
• 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)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11130592).

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.319G>A	p.Glu107Lys	missense	Exon 1 of 4	NP_940932.2
	MXRA7	NM_001008528.3		c.319G>A	p.Glu107Lys	missense	Exon 1 of 4	NP_001008528.1	P84157-1
	MXRA7	NM_001008529.3		c.319G>A	p.Glu107Lys	missense	Exon 1 of 5	NP_001008529.1	P84157-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MXRA7	ENST00000449428.7	TSL:1 MANE Select	c.319G>A	p.Glu107Lys	missense	Exon 1 of 4	ENSP00000391466.1	P84157-2
	MXRA7	ENST00000355797.7	TSL:2	c.319G>A	p.Glu107Lys	missense	Exon 1 of 4	ENSP00000348050.2	P84157-1
	MXRA7	ENST00000375036.6	TSL:2	c.319G>A	p.Glu107Lys	missense	Exon 1 of 5	ENSP00000364176.1	P84157-3

Frequencies

GnomAD3 genomes AF: 0.00000660 AC: 1 AN: 151614 Hom.: 0 Cov.: 30

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000167 AC: 1 AN: 59834 AF XY: 0.0000286

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: 0.0000470

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000487 AC: 6 AN: 1232030 Hom.: 0 Cov.: 30 AF XY: 0.00000825 AC XY: 5 AN XY: 605874

African (AFR) AF: 0.00 AC: 0 AN: 25026

American (AMR) AF: 0.00 AC: 0 AN: 20772

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20002

East Asian (EAS) AF: 0.0000771 AC: 2 AN: 25948

South Asian (SAS) AF: 0.00 AC: 0 AN: 61292

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29326

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3442

European-Non Finnish (NFE) AF: 0.00000401 AC: 4 AN: 996844

Other (OTH) AF: 0.00 AC: 0 AN: 49378

GnomAD4 genome AF: 0.00000660 AC: 1 AN: 151614 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 74046

African (AFR) AF: 0.00 AC: 0 AN: 41350

American (AMR) AF: 0.00 AC: 0 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5142

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10464

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67800

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000375 AC: 2

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	0.10
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0065	T
Eigen	Benign	-0.029
Eigen_PC	Benign	-0.022
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.011
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.059
Sift	Benign	0.24	T
Sift4G	Benign	0.44	T
Polyphen		0.99	D
Vest4		0.081
MutPred		0.35		Gain of ubiquitination at E107 (P = 0.0051)
MVP		0.21
MPC		0.11
ClinPred		0.22	T
GERP RS		3.4
PromoterAI		-0.013	Neutral
Varity_R		0.19

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs762048171; hg19: chr17-74706710;