chr1-37794687-G-C

Variant names:

• chr1-37794687-G-C
• rs1646629046
• NM_001113482.2:c.505G>C

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.505G>C​(p.Glu169Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,454,526 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.000010 (0 hom.)
• Consequence: MANEAL NM_001113482.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.14
• 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=0.1081382).

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.505G>C	p.Glu169Gln	missense	Exon 1 of 4	NP_001106954.1	Q5VSG8-1
	MANEAL	NM_001031740.3		c.505G>C	p.Glu169Gln	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.505G>C	p.Glu169Gln	missense	Exon 1 of 4	ENSP00000362136.6	Q5VSG8-1
	MANEAL	ENST00000397631.7	TSL:1	c.505G>C	p.Glu169Gln	missense	Exon 1 of 4	ENSP00000380755.3	Q5VSG8-3
	MANEAL	ENST00000951301.1		c.505G>C	p.Glu169Gln	missense	Exon 1 of 5	ENSP00000621360.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1454526 Hom.: 0 Cov.: 32 AF XY: 0.0000111 AC XY: 8 AN XY: 723348

African (AFR) AF: 0.00 AC: 0 AN: 33368

American (AMR) AF: 0.00 AC: 0 AN: 44266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25996

East Asian (EAS) AF: 0.00 AC: 0 AN: 39606

South Asian (SAS) AF: 0.000128 AC: 11 AN: 85990

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49900

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1109500

Other (OTH) AF: 0.0000332 AC: 2 AN: 60154

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	0.090
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.026	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.052
FATHMM_MKL	Benign	0.54	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.0	L
PhyloP100		3.1
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.22	N
REVEL	Benign	0.019
Sift	Benign	0.38	T
Sift4G	Benign	0.56	T
Polyphen		0.17	B
Vest4		0.063
MutPred		0.14		Loss of glycosylation at S165 (P = 0.1634)
MVP		0.20
MPC		1.5
ClinPred		0.33	T
GERP RS		3.7
PromoterAI		0.028	Neutral
Varity_R		0.11
gMVP		0.44
Mutation Taster		=85/15	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

dbSNP: rs1646629046; hg19: chr1-38260359;