chr11-68903962-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002180.3(IGHMBP2):​c.10G>A​(p.Ala4Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000709 in 1,410,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. A4A) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 35)
Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

IGHMBP2
NM_002180.3 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.941
Variant links:
Genes affected
IGHMBP2 (HGNC:5542): (immunoglobulin mu DNA binding protein 2) This gene encodes a helicase superfamily member that binds a specific DNA sequence from the immunoglobulin mu chain switch region. Mutations in this gene lead to spinal muscle atrophy with respiratory distress type 1. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.07156709).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IGHMBP2NM_002180.3 linkuse as main transcriptc.10G>A p.Ala4Thr missense_variant 1/15 ENST00000255078.8
IGHMBP2XM_047426881.1 linkuse as main transcriptc.10G>A p.Ala4Thr missense_variant 1/15
IGHMBP2XM_017017671.3 linkuse as main transcriptc.10G>A p.Ala4Thr missense_variant 1/12
IGHMBP2XM_005273976.3 linkuse as main transcriptc.10G>A p.Ala4Thr missense_variant 1/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IGHMBP2ENST00000255078.8 linkuse as main transcriptc.10G>A p.Ala4Thr missense_variant 1/151 NM_002180.3 P1

Frequencies

GnomAD3 genomes
Cov.:
35
GnomAD4 exome
AF:
7.09e-7
AC:
1
AN:
1410884
Hom.:
0
Cov.:
43
AF XY:
0.00000143
AC XY:
1
AN XY:
697666
show subpopulations
Gnomad4 AFR exome
AF:
0.00
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:
9.21e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
35
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingARUP Laboratories, Molecular Genetics and Genomics, ARUP LaboratoriesNov 02, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.089
BayesDel_addAF
Benign
0.0026
T
BayesDel_noAF
Benign
-0.23
CADD
Benign
16
DANN
Benign
0.96
DEOGEN2
Benign
0.059
T;.
Eigen
Benign
-0.83
Eigen_PC
Benign
-0.73
FATHMM_MKL
Benign
0.027
N
LIST_S2
Benign
0.61
T;T
M_CAP
Uncertain
0.13
D
MetaRNN
Benign
0.072
T;T
MetaSVM
Benign
-0.76
T
MutationAssessor
Benign
0.85
L;.
MutationTaster
Benign
1.0
N;N
PrimateAI
Uncertain
0.66
T
PROVEAN
Benign
-0.17
N;N
REVEL
Benign
0.10
Sift
Benign
0.45
T;T
Sift4G
Benign
0.44
T;T
Polyphen
0.0070
B;.
Vest4
0.074
MutPred
0.12
Gain of phosphorylation at A4 (P = 0.0899);Gain of phosphorylation at A4 (P = 0.0899);
MVP
0.89
MPC
0.19
ClinPred
0.12
T
GERP RS
1.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
Varity_R
0.095
gMVP
0.22

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1333262915; hg19: chr11-68671430; API