2-159743083-C-T

Variant names:

• chr2-159743083-C-T
• rs149235126
• NM_001282805.2:c.176C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001282805.2(MARCHF7):​c.176C>T​(p.Ala59Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00019 in 1,613,484 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00020 (0 hom.)
• Consequence: MARCHF7 NM_001282805.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.57
• Publications: 2 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.077492476).

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.176C>T	p.Ala59Val	missense	Exon 5 of 12	NP_001269734.1	Q9H992-1
	MARCHF7	NM_001376234.1		c.176C>T	p.Ala59Val	missense	Exon 4 of 11	NP_001363163.1	Q9H992-1
	MARCHF7	NM_001376235.1		c.176C>T	p.Ala59Val	missense	Exon 5 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.176C>T	p.Ala59Val	missense	Exon 5 of 12	ENSP00000386830.1	Q9H992-1
	MARCHF7	ENST00000259050.8	TSL:1	c.176C>T	p.Ala59Val	missense	Exon 3 of 10	ENSP00000259050.3	Q9H992-1
	MARCHF7	ENST00000966712.1		c.176C>T	p.Ala59Val	missense	Exon 4 of 12	ENSP00000636771.1

Frequencies

GnomAD3 genomes AF: 0.000105 AC: 16 AN: 152196 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000156 AC: 39 AN: 250600 AF XY: 0.000170

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000582

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.000462

Gnomad NFE exome AF: 0.000212

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.000198 AC: 290 AN: 1461288 Hom.: 0 Cov.: 30 AF XY: 0.000197 AC XY: 143 AN XY: 726920

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.000112 AC: 5 AN: 44618

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39680

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86134

European-Finnish (FIN) AF: 0.000656 AC: 35 AN: 53384

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.000212 AC: 236 AN: 1111752

Other (OTH) AF: 0.000182 AC: 11 AN: 60372

GnomAD4 genome AF: 0.000105 AC: 16 AN: 152196 Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12 AN XY: 74348

African (AFR) AF: 0.0000241 AC: 1 AN: 41442

American (AMR) AF: 0.00 AC: 0 AN: 15280

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

East Asian (EAS) AF: 0.000192 AC: 1 AN: 5202

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

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10606

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

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000237 Hom.: 0

Bravo AF: 0.000174

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000140 AC: 17

EpiCase AF: 0.000218

EpiControl AF: 0.000356

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	0.091
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	23
DANN	Benign	0.96
DEOGEN2	Benign	0.0097	T
Eigen	Benign	0.11
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.69	N
PhyloP100		3.6
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.44	N
REVEL	Benign	0.060
Sift	Benign	0.10	T
Sift4G	Benign	0.080	T
Polyphen		0.52	P
Vest4		0.27
MVP		0.29
MPC		0.071
ClinPred		0.045	T
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.14
gMVP		0.19
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs149235126; hg19: chr2-160599594; COSMIC: COSV99373689; COSMIC: COSV99373689;