NM_001113482.2:c.182C>A

Variant names:

• chr1-37794364-C-A
• NM_001113482.2:c.182C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001113482.2(MANEAL):​c.182C>A​(p.Ala61Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MANEAL NM_001113482.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.127
• Publications: 0 publications found

Genes affected

MANEAL (HGNC:26452): (mannosidase endo-alpha like) Predicted to enable alpha-mannosidase activity. Predicted to be located in Golgi membrane. Predicted to be integral component of membrane. Predicted to be active in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11689776).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001113482.2. 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
	MANEAL	NM_001113482.2	MANE Select	c.182C>A	p.Ala61Asp	missense	Exon 1 of 4	NP_001106954.1	Q5VSG8-1
	MANEAL	NM_001031740.3		c.182C>A	p.Ala61Asp	missense	Exon 1 of 4	NP_001026910.1	Q5VSG8-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MANEAL	ENST00000373045.11	TSL:1 MANE Select	c.182C>A	p.Ala61Asp	missense	Exon 1 of 4	ENSP00000362136.6	Q5VSG8-1
	MANEAL	ENST00000397631.7	TSL:1	c.182C>A	p.Ala61Asp	missense	Exon 1 of 4	ENSP00000380755.3	Q5VSG8-3
	MANEAL	ENST00000951301.1		c.182C>A	p.Ala61Asp	missense	Exon 1 of 5	ENSP00000621360.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 911826 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 427442

African (AFR) AF: 0.00 AC: 0 AN: 17438

American (AMR) AF: 0.00 AC: 0 AN: 3364

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7226

East Asian (EAS) AF: 0.00 AC: 0 AN: 9812

South Asian (SAS) AF: 0.00 AC: 0 AN: 18110

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9518

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1994

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 812548

Other (OTH) AF: 0.00 AC: 0 AN: 31816

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.13
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	15
DANN	Benign	0.85
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.058	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.13
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.050	N
REVEL	Benign	0.085
Sift	Benign	0.58	T
Sift4G	Benign	0.62	T
Polyphen		0.76	P
Vest4		0.13
MutPred		0.19		Gain of loop (P = 0.0312)
MVP		0.25
MPC		1.6
ClinPred		0.17	T
GERP RS		3.4
PromoterAI		-0.12	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.17
gMVP		0.53
Mutation Taster		=81/19	polymorphism

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

hg19: chr1-38260036;