15-75358495-G-A

Variant names:

• chr15-75358495-G-A
• rs1128933
• NM_006715.4:c.2370C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_006715.4(MAN2C1):​c.2370C>T​(p.Asp790Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 1,613,224 control chromosomes in the GnomAD database, including 178,303 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.37 (12553 hom., cov: 33)
  • Exomes 𝑓: 0.47 (165750 hom.)
• Consequence: MAN2C1 NM_006715.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0410
• Publications: 20 publications found

Genes affected

MAN2C1 (HGNC:6827): (mannosidase alpha class 2C member 1) Predicted to enable alpha-mannosidase activity. Predicted to be involved in oligosaccharide catabolic process. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MAN2C1 Gene-Disease associations (from GenCC):

• congenital disorder of deglycosylation 2

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Illumina, G2P

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP7: Synonymous conserved (PhyloP=-0.041 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAN2C1	NM_006715.4	c.2370C>T	p.Asp790Asp	synonymous_variant	Exon 20 of 26	ENST00000267978.10	NP_006706.2
MAN2C1	NM_001256494.2	c.2421C>T	p.Asp807Asp	synonymous_variant	Exon 20 of 26		NP_001243423.1
MAN2C1	NM_001256495.2	c.2370C>T	p.Asp790Asp	synonymous_variant	Exon 20 of 26		NP_001243424.1
MAN2C1	NM_001256496.2	c.2073C>T	p.Asp691Asp	synonymous_variant	Exon 18 of 24		NP_001243425.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAN2C1	ENST00000267978.10	c.2370C>T	p.Asp790Asp	synonymous_variant	Exon 20 of 26	1	NM_006715.4	ENSP00000267978.4

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56206 AN: 151994 Hom.: 12560 Cov.: 33

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.482

Gnomad SAS AF: 0.536

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.370

GnomAD2 exomes AF: 0.467 AC: 117155 AN: 250700 AF XY: 0.478

Gnomad AFR exome AF: 0.0975

Gnomad AMR exome AF: 0.499

Gnomad ASJ exome AF: 0.420

Gnomad EAS exome AF: 0.503

Gnomad FIN exome AF: 0.487

Gnomad NFE exome AF: 0.484

Gnomad OTH exome AF: 0.470

GnomAD4 exome AF: 0.471 AC: 688048 AN: 1461112 Hom.: 165750 Cov.: 66 AF XY: 0.474 AC XY: 344849 AN XY: 726866

African (AFR) AF: 0.0843 AC: 2824 AN: 33480

American (AMR) AF: 0.488 AC: 21827 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.423 AC: 11052 AN: 26134

East Asian (EAS) AF: 0.444 AC: 17633 AN: 39698

South Asian (SAS) AF: 0.542 AC: 46729 AN: 86256

European-Finnish (FIN) AF: 0.487 AC: 25711 AN: 52762

Middle Eastern (MID) AF: 0.398 AC: 2296 AN: 5768

European-Non Finnish (NFE) AF: 0.479 AC: 533068 AN: 1111916

Other (OTH) AF: 0.446 AC: 26908 AN: 60380

GnomAD4 genome AF: 0.369 AC: 56187 AN: 152112 Hom.: 12553 Cov.: 33 AF XY: 0.372 AC XY: 27668 AN XY: 74358

African (AFR) AF: 0.106 AC: 4394 AN: 41520

American (AMR) AF: 0.419 AC: 6406 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 1465 AN: 3468

East Asian (EAS) AF: 0.482 AC: 2487 AN: 5164

South Asian (SAS) AF: 0.535 AC: 2580 AN: 4824

European-Finnish (FIN) AF: 0.476 AC: 5030 AN: 10578

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.480 AC: 32596 AN: 67952

Other (OTH) AF: 0.365 AC: 770 AN: 2112

Alfa AF: 0.442 Hom.: 25180

Bravo AF: 0.354

Asia WGS AF: 0.477 AC: 1662 AN: 3478

EpiCase AF: 0.473

EpiControl AF: 0.479

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.40
DANN	Benign	0.85
PhyloP100		-0.041
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1128933; hg19: chr15-75650836; COSMIC: COSV51227059; COSMIC: COSV51227059;