rs771938057

Variant names:

• chr2-216369960-G-A
• rs771938057
• NM_020814.3:c.301C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-216369960-G-A
• chr2-216369960-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020814.3(MARCHF4):​c.301C>T​(p.Pro101Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000281 in 1,425,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: MARCHF4 NM_020814.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.872

Genes affected

MARCHF4 (HGNC:29269): (membrane associated ring-CH-type finger 4) MARCH4 is a member of the MARCH family of membrane-bound E3 ubiquitin ligases (EC 6.3.2.19). MARCH enzymes add ubiquitin (see MIM 191339) to target lysines in substrate proteins, thereby signaling their vesicular transport between membrane compartments. MARCH4 reduces surface accumulation of several membrane glycoproteins by directing them to the endosomal compartment (Bartee et al., 2004 [PubMed 14722266]).[supplied by OMIM, Apr 2010]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06618512).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MARCHF4	NM_020814.3	c.301C>T	p.Pro101Ser	missense_variant	Exon 1 of 4	ENST00000273067.5	NP_065865.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MARCHF4	ENST00000273067.5	c.301C>T	p.Pro101Ser	missense_variant	Exon 1 of 4	1	NM_020814.3	ENSP00000273067.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000527 AC: 1 AN: 189744 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 103284

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000355

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000281 AC: 4 AN: 1425064 Hom.: 0 Cov.: 32 AF XY: 0.00000426 AC XY: 3 AN XY: 704860

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000252

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000275

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	16
DANN	Benign	0.68
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.37
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	-0.34	N
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	0.71	N
REVEL	Benign	0.13
Sift	Benign	0.68	T
Sift4G	Benign	0.86	T
Polyphen		0.0	B
Vest4		0.21
MutPred		0.21		Loss of catalytic residue at P101 (P = 0.0024);
MVP		0.74
MPC		0.53
ClinPred		0.045	T
GERP RS		4.1
Varity_R		0.031
gMVP		0.41

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: rs771938057; hg19: chr2-217234683;