chr2-159745883-A-G

Variant names:

• chr2-159745883-A-G
• rs778493903
• NM_001282805.2:c.460A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001282805.2(MARCHF7):​c.460A>G​(p.Ile154Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,611,700 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I154L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: MARCHF7 NM_001282805.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.344
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.037944674).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282805.2. 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
	MARCHF7	NM_001282805.2	MANE Select	c.460A>G	p.Ile154Val	missense	Exon 6 of 12	NP_001269734.1	Q9H992-1
	MARCHF7	NM_001376234.1		c.460A>G	p.Ile154Val	missense	Exon 5 of 11	NP_001363163.1	Q9H992-1
	MARCHF7	NM_001376235.1		c.460A>G	p.Ile154Val	missense	Exon 6 of 12	NP_001363164.1	Q9H992-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MARCHF7	ENST00000409175.6	TSL:2 MANE Select	c.460A>G	p.Ile154Val	missense	Exon 6 of 12	ENSP00000386830.1	Q9H992-1
	MARCHF7	ENST00000259050.8	TSL:1	c.460A>G	p.Ile154Val	missense	Exon 4 of 10	ENSP00000259050.3	Q9H992-1
	MARCHF7	ENST00000966712.1		c.460A>G	p.Ile154Val	missense	Exon 5 of 12	ENSP00000636771.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152190 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000965

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000159 AC: 4 AN: 250848 AF XY: 0.0000148

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000891 AC: 13 AN: 1459510 Hom.: 0 Cov.: 30 AF XY: 0.00000964 AC XY: 7 AN XY: 726194

African (AFR) AF: 0.000299 AC: 10 AN: 33424

American (AMR) AF: 0.00 AC: 0 AN: 44636

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26096

East Asian (EAS) AF: 0.00 AC: 0 AN: 39540

South Asian (SAS) AF: 0.00 AC: 0 AN: 86132

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1110242

Other (OTH) AF: 0.0000166 AC: 1 AN: 60296

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152190 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74354

African (AFR) AF: 0.0000965 AC: 4 AN: 41444

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000132 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.59
DANN	Benign	0.68
DEOGEN2	Benign	0.063	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.038	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.11	N
PhyloP100		-0.34
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.17	N
REVEL	Benign	0.047
Sift	Benign	0.25	T
Sift4G	Benign	0.55	T
Polyphen		0.0	B
Vest4		0.19
MVP		0.093
MPC		0.032
ClinPred		0.027	T
GERP RS		-9.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.024
gMVP		0.13
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs778493903; hg19: chr2-160602394;