15-75356613-C-G

Variant names:

• chr15-75356613-C-G
• rs1219207252
• NM_006715.4:c.2730G>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_006715.4(MAN2C1):​c.2730G>C​(p.Pro910Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000284 in 1,408,508 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. Synonymous variant affecting the same amino acid position (i.e. P910P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: MAN2C1 NM_006715.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.96
• Publications: 0 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]

NEIL1 (HGNC:18448): (nei like DNA glycosylase 1) This gene is a member of the Nei endonuclease VIII-like gene family which encodes DNA glycosylases. The encoded enzyme participates in the DNA repair pathway by initiating base excision repair by removing damaged bases, primarily oxidized pyrimidines. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2012]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP7: Synonymous conserved (PhyloP=-1.96 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006715.4. 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
	MAN2C1	NM_006715.4	MANE Select	c.2730G>C	p.Pro910Pro	synonymous	Exon 23 of 26	NP_006706.2
	NEIL1	NM_024608.4	MANE Select	c.*1579C>G		3_prime_UTR	Exon 10 of 10	NP_078884.2	Q96FI4
	MAN2C1	NM_001256494.2		c.2781G>C	p.Pro927Pro	synonymous	Exon 23 of 26	NP_001243423.1	Q9NTJ4-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAN2C1	ENST00000267978.10	TSL:1 MANE Select	c.2730G>C	p.Pro910Pro	synonymous	Exon 23 of 26	ENSP00000267978.4	Q9NTJ4-1
	MAN2C1	ENST00000565683.5	TSL:1	c.2781G>C	p.Pro927Pro	synonymous	Exon 23 of 26	ENSP00000457788.1	Q9NTJ4-4
	MAN2C1	ENST00000569482.5	TSL:1	c.2730G>C	p.Pro910Pro	synonymous	Exon 23 of 26	ENSP00000455998.1	Q9NTJ4-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000284 AC: 4 AN: 1408508 Hom.: 0 Cov.: 33 AF XY: 0.00000287 AC XY: 2 AN XY: 695912

African (AFR) AF: 0.00 AC: 0 AN: 32278

American (AMR) AF: 0.00 AC: 0 AN: 36394

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25272

East Asian (EAS) AF: 0.00 AC: 0 AN: 36878

South Asian (SAS) AF: 0.00 AC: 0 AN: 80508

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4304

European-Non Finnish (NFE) AF: 0.00000369 AC: 4 AN: 1084912

Other (OTH) AF: 0.00 AC: 0 AN: 58376

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.52
DANN	Benign	0.79
PhyloP100		-2.0

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: rs1219207252; hg19: chr15-75648954;