chr20-37301396-C-T

Variant names:

• chr20-37301396-C-T
• rs2069132345
• NM_001003897.2:c.133C>T

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.133C>T​(p.Pro45Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MANBAL NM_001003897.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.75
• 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=0.07386735).

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.133C>T	p.Pro45Ser	missense	Exon 2 of 3	NP_001003897.1	Q9NQG1
	MANBAL	NM_001369742.1		c.133C>T	p.Pro45Ser	missense	Exon 4 of 5	NP_001356671.1	Q9NQG1
	MANBAL	NM_001369743.1		c.133C>T	p.Pro45Ser	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.133C>T	p.Pro45Ser	missense	Exon 2 of 3	ENSP00000362708.3	Q9NQG1
	MANBAL	ENST00000397152.7	TSL:1	c.133C>T	p.Pro45Ser	missense	Exon 4 of 5	ENSP00000380339.3	Q9NQG1
	MANBAL	ENST00000373605.7	TSL:2	c.133C>T	p.Pro45Ser	missense	Exon 3 of 4	ENSP00000362707.3	Q9NQG1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460002 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726348

African (AFR) AF: 0.00 AC: 0 AN: 33424

American (AMR) AF: 0.00 AC: 0 AN: 44628

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26064

East Asian (EAS) AF: 0.00 AC: 0 AN: 39618

South Asian (SAS) AF: 0.00 AC: 0 AN: 86062

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53342

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110806

Other (OTH) AF: 0.00 AC: 0 AN: 60292

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.096
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	18
DANN	Benign	0.26
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-1.0	T
PhyloP100		2.8
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.61	N
REVEL	Benign	0.14
Sift	Benign	1.0	T
Sift4G	Benign	0.66	T
Polyphen		0.0	B
Vest4		0.085
MutPred		0.57		Loss of glycosylation at S47 (P = 0.1096)
MVP		0.13
MPC		0.16
ClinPred		0.57	D
GERP RS		2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.031
gMVP		0.21
Mutation Taster		=88/12	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: rs2069132345; hg19: chr20-35929799;