chr1-117368190-A-G

Position:

• chr1-117368190-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006699.5(MAN1A2):​c.7A>G​(p.Thr3Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000686 in 1,457,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000069 (0 hom.)
• Consequence: MAN1A2 NM_006699.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.94

Genes affected

MAN1A2 (HGNC:6822): (mannosidase alpha class 1A member 2) Alpha-mannosidases function at different stages of N-glycan maturation in mammalian cells. See MAN2A1 (MIM 154582) for general information.[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.082214415).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAN1A2	NM_006699.5	c.7A>G	p.Thr3Ala	missense_variant	1/13	ENST00000356554.7
MAN1A2	XM_006710302.4	c.7A>G	p.Thr3Ala	missense_variant	1/14
MAN1A2	XM_011540536.4	c.7A>G	p.Thr3Ala	missense_variant	1/13
MAN1A2	XM_017000115.2	c.7A>G	p.Thr3Ala	missense_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAN1A2	ENST00000356554.7	c.7A>G	p.Thr3Ala	missense_variant	1/13	1	NM_006699.5	P1
MAN1A2	ENST00000482811.1	n.248A>G		non_coding_transcript_exon_variant	1/3	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000686 AC: 10 AN: 1457038 Hom.: 0 Cov.: 32 AF XY: 0.00000690 AC XY: 5 AN XY: 724698

Gnomad4 AFR exome AF: 0.0000603

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000720

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 20, 2023

The c.7A>G (p.T3A) alteration is located in exon 1 (coding exon 1) of the MAN1A2 gene. This alteration results from a A to G substitution at nucleotide position 7, causing the threonine (T) at amino acid position 3 to be replaced by an alanine (A). 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	Benign	0.061
BayesDel_addAF	Benign	-0.049	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.055	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.46	N
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.17	N
REVEL	Benign	0.26
Sift	Benign	0.093	T
Sift4G	Benign	0.26	T
Polyphen		0.0020	B
Vest4		0.12
MutPred		0.095		Loss of glycosylation at T3 (P = 0.012);
MVP		0.41
MPC		0.62
ClinPred		0.48	T
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.059
gMVP		0.59

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-117910812;