2-159743236-G-A

Variant names:

• chr2-159743236-G-A
• rs1704363949
• NM_001282805.2:c.329G>A

Variant summary

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

The NM_001282805.2(MARCHF7):​c.329G>A​(p.Gly110Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MARCHF7 NM_001282805.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.93

Genes affected

MARCHF7 (HGNC:17393): (membrane associated ring-CH-type finger 7) MARCH7 is a member of the MARCH family of membrane-bound E3 ubiquitin ligases (EC 6.3.2.19). MARCH proteins add ubiquitin (see MIM 191339) to target lysines in substrate proteins, thereby signaling their vesicular transport between membrane compartments (Bartee et al., 2004 [PubMed 14722266]).[supplied by OMIM, Mar 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MARCHF7	NM_001282805.2	c.329G>A	p.Gly110Asp	missense_variant	Exon 5 of 12	ENST00000409175.6	NP_001269734.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MARCHF7	ENST00000409175.6	c.329G>A	p.Gly110Asp	missense_variant	Exon 5 of 12	2	NM_001282805.2	ENSP00000386830.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 29, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.329G>A (p.G110D) alteration is located in exon 3 (coding exon 2) of the MARCH7 gene. This alteration results from a G to A substitution at nucleotide position 329, causing the glycine (G) at amino acid position 110 to be replaced by an aspartic acid (D). 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	Benign	0.19
BayesDel_addAF	Uncertain	0.077	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.019	T;T;T;.
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D;.;D;D
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.47	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	.;L;L;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.2	N;N;N;N
REVEL	Benign	0.15
Sift	Uncertain	0.0020	D;D;D;D
Sift4G	Benign	0.20	T;T;T;T
Polyphen		1.0	D;D;D;.
Vest4		0.78
MutPred		0.22		Gain of relative solvent accessibility (P = 0.0082);Gain of relative solvent accessibility (P = 0.0082);Gain of relative solvent accessibility (P = 0.0082);.;
MVP		0.33
MPC		0.29
ClinPred		0.95	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.32
gMVP		0.20

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: rs1704363949; hg19: chr2-160599747;