15-90905642-T-C

Variant names:

• chr15-90905642-T-C
• NM_006122.4:c.454T>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006122.4(MAN2A2):​c.454T>C​(p.Phe152Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MAN2A2 NM_006122.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.97

Genes affected

MAN2A2 (HGNC:6825): (mannosidase alpha class 2A member 2) Predicted to enable alpha-mannosidase activity. Predicted to be involved in N-glycan processing and protein deglycosylation. Predicted to be integral component of membrane. Predicted to be active in Golgi membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAN2A2	NM_006122.4	c.454T>C	p.Phe152Leu	missense_variant	Exon 4 of 23	ENST00000559717.6	NP_006113.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAN2A2	ENST00000559717.6	c.454T>C	p.Phe152Leu	missense_variant	Exon 4 of 23	2	NM_006122.4	ENSP00000452948.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 08, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.454T>C (p.F152L) alteration is located in exon 3 (coding exon 3) of the MAN2A2 gene. This alteration results from a T to C substitution at nucleotide position 454, causing the phenylalanine (F) at amino acid position 152 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.61	D;D
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	.;D
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.48	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M;M
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-3.7	.;D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0090	.;D
Sift4G	Benign	0.13	T;T
Polyphen		0.32	B;B
Vest4		0.60
MutPred		0.65		Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);
MVP		0.55
MPC		0.53
ClinPred		0.98	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.48
gMVP		0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-91448872;