chr20-37301412-C-T

Variant names:

• chr20-37301412-C-T
• rs138745176
• NM_001003897.2:c.149C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001003897.2(MANBAL):​c.149C>T​(p.Ala50Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000138 in 1,610,476 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00064 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000086 (0 hom.)
• Consequence: MANBAL NM_001003897.2 missense, splice_region
• Scores: Splicing: ADA: 0.001224
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.398
• Publications: 3 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006928891).

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.149C>T	p.Ala50Val	missense splice_region	Exon 2 of 3	NP_001003897.1	Q9NQG1
	MANBAL	NM_001369742.1		c.149C>T	p.Ala50Val	missense splice_region	Exon 4 of 5	NP_001356671.1	Q9NQG1
	MANBAL	NM_001369743.1		c.149C>T	p.Ala50Val	missense splice_region	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.149C>T	p.Ala50Val	missense splice_region	Exon 2 of 3	ENSP00000362708.3	Q9NQG1
	MANBAL	ENST00000397152.7	TSL:1	c.149C>T	p.Ala50Val	missense splice_region	Exon 4 of 5	ENSP00000380339.3	Q9NQG1
	MANBAL	ENST00000373605.7	TSL:2	c.149C>T	p.Ala50Val	missense splice_region	Exon 3 of 4	ENSP00000362707.3	Q9NQG1

Frequencies

GnomAD3 genomes AF: 0.000644 AC: 98 AN: 152152 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00181

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000851

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.000959

GnomAD2 exomes AF: 0.000184 AC: 46 AN: 249518 AF XY: 0.000156

Gnomad AFR exome AF: 0.00180

Gnomad AMR exome AF: 0.000235

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000549

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000619

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000857 AC: 125 AN: 1458206 Hom.: 0 Cov.: 30 AF XY: 0.0000744 AC XY: 54 AN XY: 725506

African (AFR) AF: 0.00147 AC: 49 AN: 33346

American (AMR) AF: 0.000472 AC: 21 AN: 44506

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25988

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39558

South Asian (SAS) AF: 0.0000233 AC: 2 AN: 85826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53274

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.0000360 AC: 40 AN: 1109744

Other (OTH) AF: 0.000199 AC: 12 AN: 60210

GnomAD4 genome AF: 0.000644 AC: 98 AN: 152270 Hom.: 0 Cov.: 32 AF XY: 0.000645 AC XY: 48 AN XY: 74458

African (AFR) AF: 0.00180 AC: 75 AN: 41562

American (AMR) AF: 0.000850 AC: 13 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68014

Other (OTH) AF: 0.000949 AC: 2 AN: 2108

Alfa AF: 0.0191 Hom.: 2354

Bravo AF: 0.000752

ESP6500AA AF: 0.00204 AC: 9

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000214 AC: 26

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	0.060
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	13
DANN	Benign	0.89
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.0069	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.40
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.010	N
REVEL	Benign	0.028
Sift	Benign	0.58	T
Sift4G	Benign	0.33	T
Polyphen		0.0	B
Vest4		0.074
MVP		0.076
MPC		0.13
ClinPred		0.0018	T
GERP RS		-2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.015
gMVP		0.21
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0012
dbscSNV1_RF	Benign	0.014
SpliceAI score (max)		0.11		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: rs138745176; hg19: chr20-35929815; COSMIC: COSV65311437;