rs3750912

chr11-72015166-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_006185.4(NUMA1):c.2337G>A(p.Gln779=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0123 in 1,613,496 control chromosomes in the GnomAD database, including 319 homozygotes. 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: 𝑓 0.025 (91 hom., cov: 33)
  • Exomes 𝑓: 0.011 (228 hom.)
• Consequence: NUMA1 NM_006185.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.671

Genes affected

NUMA1 (HGNC:8059): (nuclear mitotic apparatus protein 1) This gene encodes a large protein that forms a structural component of the nuclear matrix. The encoded protein interacts with microtubules and plays a role in the formation and organization of the mitotic spindle during cell division. Chromosomal translocation of this gene with the RARA (retinoic acid receptor, alpha) gene on chromosome 17 have been detected in patients with acute promyelocytic leukemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2013]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP7: Synonymous conserved (PhyloP=0.671 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUMA1	NM_006185.4	c.2337G>A	p.Gln779=	synonymous_variant	15/27	ENST00000393695.8
LOC100128494	NR_104178.1	n.876C>T		non_coding_transcript_exon_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUMA1	ENST00000393695.8	c.2337G>A	p.Gln779=	synonymous_variant	15/27	1	NM_006185.4	P2
	ENST00000502284.1	n.876C>T		non_coding_transcript_exon_variant	1/4	2

Frequencies

GnomAD3 genomes AF: 0.0251 AC: 3829 AN: 152264 Hom.: 90 Cov.: 33

Gnomad AFR AF: 0.0620

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0120

Gnomad ASJ AF: 0.00980

Gnomad EAS AF: 0.0660

Gnomad SAS AF: 0.0209

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00748

Gnomad OTH AF: 0.0263

GnomAD3 exomes AF: 0.0154 AC: 3834 AN: 249144 Hom.: 83 AF XY: 0.0145 AC XY: 1952 AN XY: 134828

Gnomad AFR exome AF: 0.0657

Gnomad AMR exome AF: 0.00495

Gnomad ASJ exome AF: 0.0117

Gnomad EAS exome AF: 0.0585

Gnomad SAS exome AF: 0.0159

Gnomad FIN exome AF: 0.00103

Gnomad NFE exome AF: 0.00742

Gnomad OTH exome AF: 0.0118

GnomAD4 exome AF: 0.0110 AC: 16047 AN: 1461114 Hom.: 228 Cov.: 35 AF XY: 0.0109 AC XY: 7941 AN XY: 726884

Gnomad4 AFR exome AF: 0.0658

Gnomad4 AMR exome AF: 0.00648

Gnomad4 ASJ exome AF: 0.0119

Gnomad4 EAS exome AF: 0.0580

Gnomad4 SAS exome AF: 0.0164

Gnomad4 FIN exome AF: 0.00135

Gnomad4 NFE exome AF: 0.00757

Gnomad4 OTH exome AF: 0.0161

GnomAD4 genome AF: 0.0251 AC: 3832 AN: 152382 Hom.: 91 Cov.: 33 AF XY: 0.0249 AC XY: 1852 AN XY: 74522

Gnomad4 AFR AF: 0.0618

Gnomad4 AMR AF: 0.0120

Gnomad4 ASJ AF: 0.00980

Gnomad4 EAS AF: 0.0661

Gnomad4 SAS AF: 0.0207

Gnomad4 FIN AF: 0.000659

Gnomad4 NFE AF: 0.00748

Gnomad4 OTH AF: 0.0293

Alfa AF: 0.0152 Hom.: 33

Bravo AF: 0.0286

Asia WGS AF: 0.0510 AC: 176 AN: 3478

EpiCase AF: 0.00774

EpiControl AF: 0.00907

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	15
Dann	Benign	0.61

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

Other links and lift over

dbSNP: rs3750912; hg19: chr11-71726212; COSMIC: COSV61185766; COSMIC: COSV61185766;