chr17-62725033-C-G

Variant names:

• chr17-62725033-C-G
• rs904173499
• NM_152598.4:c.2009G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_152598.4(MARCHF10):​c.2009G>C​(p.Ser670Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,457,464 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 Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MARCHF10 NM_152598.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.47
• 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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04766932).
• BP6: Variant 17-62725033-C-G is Benign according to our data. Variant chr17-62725033-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3870536.Status of the report is criteria_provided_single_submitter, 1 stars.

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.2009G>C	p.Ser670Thr	missense	Exon 7 of 11	NP_689811.2	A0A140VKA1
	MARCHF10	NM_001288779.2		c.2123G>C	p.Ser708Thr	missense	Exon 8 of 12	NP_001275708.1	J3KTN9
	MARCHF10	NM_001100875.3		c.2009G>C	p.Ser670Thr	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.2009G>C	p.Ser670Thr	missense	Exon 7 of 11	ENSP00000311496.5	Q8NA82
	MARCHF10	ENST00000583600.5	TSL:1	c.2123G>C	p.Ser708Thr	missense	Exon 8 of 12	ENSP00000463080.1	J3KTN9
	MARCHF10	ENST00000456609.6	TSL:1	c.2009G>C	p.Ser670Thr	missense	Exon 7 of 11	ENSP00000416177.2	Q8NA82

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1457464 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 724992

African (AFR) AF: 0.0000300 AC: 1 AN: 33308

American (AMR) AF: 0.00 AC: 0 AN: 43688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26054

East Asian (EAS) AF: 0.00 AC: 0 AN: 39422

South Asian (SAS) AF: 0.00 AC: 0 AN: 85154

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

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110434

Other (OTH) AF: 0.00 AC: 0 AN: 60250

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.068
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	10
DANN	Benign	0.74
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.18	N
PhyloP100		1.5
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.040	N
REVEL	Benign	0.067
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.17
MutPred		0.39		Gain of catalytic residue at S670 (P = 0.0441)
MVP		0.22
MPC		0.12
ClinPred		0.024	T
GERP RS		2.3
Varity_R		0.039
gMVP		0.44

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: rs904173499; hg19: chr17-60802394; COSMIC: COSV60887883;