rs751910797

Variant names:

• chr11-68903959-T-C
• NM_002180.3:c.7T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-68903959-T-C
• chr11-68903959-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002180.3(IGHMBP2):​c.7T>C​(p.Ser3Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000708 in 1,412,122 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 35)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: IGHMBP2 NM_002180.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.254

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]

MRPL21 (HGNC:14479): (mitochondrial ribosomal protein L21) Mammalian mitochondrial ribosomal proteins are encoded by nuclear genes and help in protein synthesis within the mitochondrion. Mitochondrial ribosomes (mitoribosomes) consist of a small 28S subunit and a large 39S subunit. They have an estimated 75% protein to rRNA composition compared to prokaryotic ribosomes, where this ratio is reversed. Another difference between mammalian mitoribosomes and prokaryotic ribosomes is that the latter contain a 5S rRNA. Among different species, the proteins comprising the mitoribosome differ greatly in sequence, and sometimes in biochemical properties, which prevents easy recognition by sequence homology. This gene encodes a 39S subunit protein. Multiple transcript variants encoding different isoforms were identified through sequence analysis although some may be subject to nonsense-mediated decay (NMD). [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27061135).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGHMBP2	NM_002180.3	c.7T>C	p.Ser3Pro	missense_variant	Exon 1 of 15	ENST00000255078.8	NP_002171.2
MRPL21	NM_181514.2	c.-149A>G		upstream_gene_variant		ENST00000362034.7	NP_852615.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGHMBP2	ENST00000255078.8	c.7T>C	p.Ser3Pro	missense_variant	Exon 1 of 15	1	NM_002180.3	ENSP00000255078.4
MRPL21	ENST00000362034.7	c.-149A>G		upstream_gene_variant		1	NM_181514.2	ENSP00000354580.2

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome AF: 7.08e-7 AC: 1 AN: 1412122 Hom.: 0 Cov.: 45 AF XY: 0.00 AC XY: 0 AN XY: 698446

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: 9.20e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.088	T;.
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.63	T;T
M_CAP	Pathogenic	0.55	D
MetaRNN	Benign	0.27	T;T
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Benign	1.4	L;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.86	N;N
REVEL	Uncertain	0.33
Sift	Uncertain	0.018	D;D
Sift4G	Benign	0.35	T;T
Polyphen		0.47	P;.
Vest4		0.37
MutPred		0.22		Loss of phosphorylation at S3 (P = 0.0243);Loss of phosphorylation at S3 (P = 0.0243);
MVP		0.93
MPC		0.47
ClinPred		0.49	T
GERP RS		2.9
Varity_R		0.46
gMVP		0.37

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: chr11-68671427;