NM_020379.4:c.1047+198G>A

Variant names:

• chr1-25758907-G-A
• rs12130495
• NM_020379.4:c.1047+198G>A

Variant summary

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

The NM_020379.4(MAN1C1):​c.1047+198G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000513 in 585,116 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000046 (0 hom.)
• Consequence: MAN1C1 NM_020379.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0320
• Publications: 2 publications found

Genes affected

MAN1C1 (HGNC:19080): (mannosidase alpha class 1C member 1) Predicted to enable mannosyl-oligosaccharide 1,2-alpha-mannosidase activity. Predicted to be involved in N-glycan processing. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAN1C1	NM_020379.4	c.1047+198G>A		intron_variant	Intron 6 of 11	ENST00000374332.9	NP_065112.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAN1C1	ENST00000374332.9	c.1047+198G>A		intron_variant	Intron 6 of 11	1	NM_020379.4	ENSP00000363452.4
MAN1C1	ENST00000473891.1	n.643G>A		non_coding_transcript_exon_variant	Exon 5 of 5	4
MAN1C1	ENST00000263979.7	c.507+198G>A		intron_variant	Intron 7 of 12	5		ENSP00000263979.3
MAN1C1	ENST00000374329.1	c.360+198G>A		intron_variant	Intron 5 of 10	2		ENSP00000363449.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151948 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000462 AC: 2 AN: 433168 Hom.: 0 Cov.: 3 AF XY: 0.00 AC XY: 0 AN XY: 229398

African (AFR) AF: 0.0000822 AC: 1 AN: 12170

American (AMR) AF: 0.00 AC: 0 AN: 18830

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13074

East Asian (EAS) AF: 0.00 AC: 0 AN: 29476

South Asian (SAS) AF: 0.00 AC: 0 AN: 46204

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27758

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3080

European-Non Finnish (NFE) AF: 0.00000388 AC: 1 AN: 257618

Other (OTH) AF: 0.00 AC: 0 AN: 24958

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151948 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74246

African (AFR) AF: 0.00 AC: 0 AN: 41398

American (AMR) AF: 0.00 AC: 0 AN: 15278

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67840

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 9

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.3
DANN	Benign	0.57
PhyloP100		-0.032

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: rs12130495; hg19: chr1-26085398;