chr17-62725040-A-G

Variant names:

• chr17-62725040-A-G
• rs377320844
• NM_152598.4:c.2002T>C

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_152598.4(MARCHF10):​c.2002T>C​(p.Ser668Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000147 in 1,609,238 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00016 (0 hom.)
• Consequence: MARCHF10 NM_152598.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.19
• Publications: 0 publications found

Genes affected

MARCHF10 (HGNC:26655): (membrane associated ring-CH-type finger 10) MARCH10 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 (Morokuma et al., 2007 [PubMed 17604280]).[supplied by OMIM, Apr 2010]

MARCHF10-AS1 (HGNC:58173):

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.34964746).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152598.4. 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
	MARCHF10	NM_152598.4	MANE Select	c.2002T>C	p.Ser668Pro	missense	Exon 7 of 11	NP_689811.2	A0A140VKA1
	MARCHF10	NM_001288779.2		c.2116T>C	p.Ser706Pro	missense	Exon 8 of 12	NP_001275708.1	J3KTN9
	MARCHF10	NM_001100875.3		c.2002T>C	p.Ser668Pro	missense	Exon 7 of 11	NP_001094345.1	Q8NA82

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MARCHF10	ENST00000311269.10	TSL:2 MANE Select	c.2002T>C	p.Ser668Pro	missense	Exon 7 of 11	ENSP00000311496.5	Q8NA82
	MARCHF10	ENST00000583600.5	TSL:1	c.2116T>C	p.Ser706Pro	missense	Exon 8 of 12	ENSP00000463080.1	J3KTN9
	MARCHF10	ENST00000456609.6	TSL:1	c.2002T>C	p.Ser668Pro	missense	Exon 7 of 11	ENSP00000416177.2	Q8NA82

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 152140 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

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: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000325 AC: 8 AN: 245918 AF XY: 0.0000150

Gnomad AFR exome AF: 0.0000623

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000445

Gnomad OTH exome AF: 0.000339

GnomAD4 exome AF: 0.000156 AC: 227 AN: 1457098 Hom.: 0 Cov.: 31 AF XY: 0.000131 AC XY: 95 AN XY: 724820

African (AFR) AF: 0.00 AC: 0 AN: 33286

American (AMR) AF: 0.00 AC: 0 AN: 43588

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26032

East Asian (EAS) AF: 0.00 AC: 0 AN: 39390

South Asian (SAS) AF: 0.00 AC: 0 AN: 85116

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.000197 AC: 219 AN: 1110290

Other (OTH) AF: 0.000133 AC: 8 AN: 60246

GnomAD4 genome AF: 0.0000592 AC: 9 AN: 152140 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74316

African (AFR) AF: 0.0000724 AC: 3 AN: 41426

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68012

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

Alfa AF: 0.000135 Hom.: 0

Bravo AF: 0.0000604

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000330 AC: 4

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	Pathogenic	0.70
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.27
CADD	Pathogenic	27
DANN	Benign	0.97
DEOGEN2	Benign	0.094	T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	2.0	M
PhyloP100		2.2
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.19
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.012	D
Polyphen		1.0	D
Vest4		0.57
MVP		0.67
MPC		0.68
ClinPred		0.49	T
GERP RS		5.4
Varity_R		0.86
gMVP		0.77
Mutation Taster		=85/15	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: rs377320844; hg19: chr17-60802401;