20-37301405-C-A

Variant names:

• chr20-37301405-C-A
• rs746257147
• NM_001003897.2:c.142C>A

Variant summary

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

The NM_001003897.2(MANBAL):​c.142C>A​(p.His48Asn) 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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H48D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MANBAL NM_001003897.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.71
• Publications: 0 publications found

Genes affected

MANBAL (HGNC:15799): (mannosidase beta like) Predicted to be integral component of membrane. [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=0.08106589).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001003897.2. 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
	MANBAL	NM_001003897.2	MANE Select	c.142C>A	p.His48Asn	missense	Exon 2 of 3	NP_001003897.1	Q9NQG1
	MANBAL	NM_001369742.1		c.142C>A	p.His48Asn	missense	Exon 4 of 5	NP_001356671.1	Q9NQG1
	MANBAL	NM_001369743.1		c.142C>A	p.His48Asn	missense	Exon 3 of 4	NP_001356672.1	Q9NQG1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MANBAL	ENST00000373606.8	TSL:1 MANE Select	c.142C>A	p.His48Asn	missense	Exon 2 of 3	ENSP00000362708.3	Q9NQG1
	MANBAL	ENST00000397152.7	TSL:1	c.142C>A	p.His48Asn	missense	Exon 4 of 5	ENSP00000380339.3	Q9NQG1
	MANBAL	ENST00000373605.7	TSL:2	c.142C>A	p.His48Asn	missense	Exon 3 of 4	ENSP00000362707.3	Q9NQG1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	11
DANN	Benign	0.86
DEOGEN2	Benign	0.045	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.7
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.18
Sift	Benign	0.18	T
Sift4G	Benign	0.36	T
Polyphen		0.011	B
Vest4		0.20
MutPred		0.60		Gain of relative solvent accessibility (P = 0.0275)
MVP		0.10
MPC		0.17
ClinPred		0.043	T
GERP RS		0.027
Varity_R		0.039
gMVP		0.40
Mutation Taster		=90/10	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: rs746257147; hg19: chr20-35929808;