rs141992383

Variant names:

• chr17-62705543-A-G
• rs141992383
• NM_152598.4:c.2367T>C

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_152598.4(MARCHF10):​c.2367T>C​(p.Asn789Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000595 in 1,614,010 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00034 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000030 (0 hom.)
• Consequence: MARCHF10 NM_152598.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.771
• 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: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 17-62705543-A-G is Benign according to our data. Variant chr17-62705543-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 916237.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.771 with no splicing effect.

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.2367T>C	p.Asn789Asn	synonymous	Exon 10 of 11	NP_689811.2	A0A140VKA1
	MARCHF10	NM_001288779.2		c.2481T>C	p.Asn827Asn	synonymous	Exon 11 of 12	NP_001275708.1	J3KTN9
	MARCHF10	NM_001100875.3		c.2367T>C	p.Asn789Asn	synonymous	Exon 10 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.2367T>C	p.Asn789Asn	synonymous	Exon 10 of 11	ENSP00000311496.5	Q8NA82
	MARCHF10	ENST00000583600.5	TSL:1	c.2481T>C	p.Asn827Asn	synonymous	Exon 11 of 12	ENSP00000463080.1	J3KTN9
	MARCHF10	ENST00000456609.6	TSL:1	c.2367T>C	p.Asn789Asn	synonymous	Exon 10 of 11	ENSP00000416177.2	Q8NA82

Frequencies

GnomAD3 genomes AF: 0.000342 AC: 52 AN: 152032 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00111

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

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: 0.000956

GnomAD2 exomes AF: 0.0000597 AC: 15 AN: 251430 AF XY: 0.0000589

Gnomad AFR exome AF: 0.000861

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 0.0000301 AC: 44 AN: 1461860 Hom.: 0 Cov.: 33 AF XY: 0.0000248 AC XY: 18 AN XY: 727242

African (AFR) AF: 0.00114 AC: 38 AN: 33476

American (AMR) AF: 0.0000447 AC: 2 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111996

Other (OTH) AF: 0.0000497 AC: 3 AN: 60394

GnomAD4 genome AF: 0.000342 AC: 52 AN: 152150 Hom.: 0 Cov.: 32 AF XY: 0.000376 AC XY: 28 AN XY: 74396

African (AFR) AF: 0.00111 AC: 46 AN: 41504

American (AMR) AF: 0.000262 AC: 4 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67988

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.000228 Hom.: 0

Bravo AF: 0.000314

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	6.5
DANN	Benign	0.87
PhyloP100		0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs141992383; hg19: chr17-60782904;