5-177332169-C-T

Variant names:

• chr5-177332169-C-T
• rs150674852
• NM_006816.3:c.988G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_006816.3(LMAN2):​c.988G>A​(p.Ala330Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00694 in 1,613,636 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0054 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0071 (46 hom.)
• Consequence: LMAN2 NM_006816.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.15
• Publications: 11 publications found

Genes affected

LMAN2 (HGNC:16986): (lectin, mannose binding 2) This gene encodes a type I transmembrane lectin that shuttles between the endoplasmic reticulum, the Golgi apparatus and the plasma membrane. The encoded protein binds high mannose type glycoproteins and may facilitate their sorting, trafficking and quality control. [provided by RefSeq, Oct 2008]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0093584955).
• BP6: Variant 5-177332169-C-T is Benign according to our data. Variant chr5-177332169-C-T is described in ClinVar as Benign. ClinVar VariationId is 711392.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 46 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006816.3. 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
	LMAN2	NM_006816.3	MANE Select	c.988G>A	p.Ala330Thr	missense	Exon 8 of 8	NP_006807.1	Q12907

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMAN2	ENST00000303127.12	TSL:1 MANE Select	c.988G>A	p.Ala330Thr	missense	Exon 8 of 8	ENSP00000303366.7	Q12907
	LMAN2	ENST00000883396.1		c.1114G>A	p.Ala372Thr	missense	Exon 9 of 9	ENSP00000553455.1
	LMAN2	ENST00000883394.1		c.1018G>A	p.Ala340Thr	missense	Exon 8 of 8	ENSP00000553453.1

Frequencies

GnomAD3 genomes AF: 0.00537 AC: 817 AN: 152208 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00142

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.00288

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00517

Gnomad FIN AF: 0.00207

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00817

Gnomad OTH AF: 0.00621

GnomAD2 exomes AF: 0.00533 AC: 1328 AN: 248952 AF XY: 0.00542

Gnomad AFR exome AF: 0.00114

Gnomad AMR exome AF: 0.00160

Gnomad ASJ exome AF: 0.0113

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00279

Gnomad NFE exome AF: 0.00796

Gnomad OTH exome AF: 0.00461

GnomAD4 exome AF: 0.00711 AC: 10386 AN: 1461310 Hom.: 46 Cov.: 31 AF XY: 0.00711 AC XY: 5172 AN XY: 726982

African (AFR) AF: 0.00119 AC: 40 AN: 33478

American (AMR) AF: 0.00197 AC: 88 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.0123 AC: 320 AN: 26120

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39694

South Asian (SAS) AF: 0.00540 AC: 466 AN: 86254

European-Finnish (FIN) AF: 0.00325 AC: 172 AN: 52980

Middle Eastern (MID) AF: 0.00573 AC: 33 AN: 5764

European-Non Finnish (NFE) AF: 0.00797 AC: 8864 AN: 1111930

Other (OTH) AF: 0.00666 AC: 402 AN: 60380

GnomAD4 genome AF: 0.00536 AC: 816 AN: 152326 Hom.: 0 Cov.: 33 AF XY: 0.00464 AC XY: 346 AN XY: 74490

African (AFR) AF: 0.00142 AC: 59 AN: 41564

American (AMR) AF: 0.00287 AC: 44 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0115 AC: 40 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00497 AC: 24 AN: 4832

European-Finnish (FIN) AF: 0.00207 AC: 22 AN: 10624

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00817 AC: 556 AN: 68024

Other (OTH) AF: 0.00614 AC: 13 AN: 2116

Alfa AF: 0.00692 Hom.: 10

Bravo AF: 0.00549

TwinsUK AF: 0.00971 AC: 36

ALSPAC AF: 0.0112 AC: 43

ESP6500AA AF: 0.00204 AC: 9

ESP6500EA AF: 0.00896 AC: 77

ExAC AF: 0.00536 AC: 651

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.00807

EpiControl AF: 0.00705

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.083	T
Eigen	Benign	0.0029
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.0094	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.2	L
PhyloP100		3.1
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-0.87	N
REVEL	Benign	0.10
Sift	Benign	0.40	T
Sift4G	Benign	0.73	T
Polyphen		0.31	B
Vest4		0.48
MVP		0.62
MPC		0.44
ClinPred		0.0076	T
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.075
gMVP		0.54
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: rs150674852; hg19: chr5-176759170; COSMIC: COSV57424569; COSMIC: COSV57424569;