17-76710745-G-A

Variant names:

• chr17-76710745-G-A
• rs955913436
• NM_198530.4:c.202C>T

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.202C>T​(p.Pro68Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000911 in 1,108,770 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: MXRA7 NM_198530.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.223
• 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: 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=0.0636155).

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.202C>T	p.Pro68Ser	missense	Exon 1 of 4	NP_940932.2
	MXRA7	NM_001008528.3		c.202C>T	p.Pro68Ser	missense	Exon 1 of 4	NP_001008528.1	P84157-1
	MXRA7	NM_001008529.3		c.202C>T	p.Pro68Ser	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.202C>T	p.Pro68Ser	missense	Exon 1 of 4	ENSP00000391466.1	P84157-2
	MXRA7	ENST00000355797.7	TSL:2	c.202C>T	p.Pro68Ser	missense	Exon 1 of 4	ENSP00000348050.2	P84157-1
	MXRA7	ENST00000375036.6	TSL:2	c.202C>T	p.Pro68Ser	missense	Exon 1 of 5	ENSP00000364176.1	P84157-3

Frequencies

GnomAD3 genomes AF: 0.0000202 AC: 3 AN: 148238 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: 0.0000450

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000102 AC: 98 AN: 960532 Hom.: 0 Cov.: 16 AF XY: 0.000110 AC XY: 50 AN XY: 452922

African (AFR) AF: 0.000104 AC: 2 AN: 19226

American (AMR) AF: 0.00 AC: 0 AN: 5754

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10608

East Asian (EAS) AF: 0.00 AC: 0 AN: 19002

South Asian (SAS) AF: 0.00 AC: 0 AN: 17576

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 17120

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2420

European-Non Finnish (NFE) AF: 0.000113 AC: 94 AN: 832364

Other (OTH) AF: 0.0000549 AC: 2 AN: 36462

GnomAD4 genome AF: 0.0000202 AC: 3 AN: 148238 Hom.: 0 Cov.: 30 AF XY: 0.0000138 AC XY: 1 AN XY: 72268

African (AFR) AF: 0.00 AC: 0 AN: 40910

American (AMR) AF: 0.00 AC: 0 AN: 14932

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3424

East Asian (EAS) AF: 0.00 AC: 0 AN: 5094

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9136

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000450 AC: 3 AN: 66650

Other (OTH) AF: 0.00 AC: 0 AN: 2046

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

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	0.072
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	9.9
DANN	Benign	0.89
DEOGEN2	Benign	0.054	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.064	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L
PhyloP100		-0.22
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.017
Sift	Benign	0.059	T
Sift4G	Uncertain	0.035	D
Polyphen		0.012	B
Vest4		0.071
MutPred		0.31		Gain of phosphorylation at P68 (P = 0.0039)
MVP		0.014
MPC		0.10
ClinPred		0.10	T
GERP RS		-1.0
PromoterAI		-0.013	Neutral
Varity_R		0.028
Mutation Taster		=98/2	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: rs955913436; hg19: chr17-74706827;