rs1031381

Variant names:

• chr11-134218788-G-A
• rs1031381
• NM_015261.3:c.220-1690C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-134218788-G-A
• chr11-134218788-G-C
• chr11-134218788-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015261.3(NCAPD3):​c.220-1690C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 151,822 control chromosomes in the GnomAD database, including 10,728 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 0.36 (10728 hom., cov: 32)
• Consequence: NCAPD3 NM_015261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00700
• Publications: 18 publications found

Genes affected

NCAPD3 (HGNC:28952): (non-SMC condensin II complex subunit D3) Condensin complexes I and II play essential roles in mitotic chromosome assembly and segregation. Both condensins contain 2 invariant structural maintenance of chromosome (SMC) subunits, SMC2 (MIM 605576) and SMC4 (MIM 605575), but they contain different sets of non-SMC subunits. NCAPD3 is 1 of 3 non-SMC subunits that define condensin II (Ono et al., 2003 [PubMed 14532007]).[supplied by OMIM, Mar 2008]

NCAPD3 Gene-Disease associations (from GenCC):

• autosomal recessive primary microcephaly

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• microcephaly 22, primary, autosomal recessive

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCAPD3	NM_015261.3	c.220-1690C>T		intron_variant	Intron 2 of 34	ENST00000534548.7	NP_056076.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCAPD3	ENST00000534548.7	c.220-1690C>T		intron_variant	Intron 2 of 34	1	NM_015261.3	ENSP00000433681.3

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55050 AN: 151704 Hom.: 10723 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.545

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.393

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.363 AC: 55073 AN: 151822 Hom.: 10728 Cov.: 32 AF XY: 0.367 AC XY: 27223 AN XY: 74184

African (AFR) AF: 0.223 AC: 9210 AN: 41368

American (AMR) AF: 0.480 AC: 7327 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.392 AC: 1360 AN: 3466

East Asian (EAS) AF: 0.545 AC: 2809 AN: 5152

South Asian (SAS) AF: 0.494 AC: 2381 AN: 4816

European-Finnish (FIN) AF: 0.388 AC: 4084 AN: 10538

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.391 AC: 26520 AN: 67900

Other (OTH) AF: 0.392 AC: 827 AN: 2108

Alfa AF: 0.393 Hom.: 57599

Bravo AF: 0.365

Asia WGS AF: 0.513 AC: 1787 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.42
PhyloP100		0.0070
Mutation Taster		=100/0	polymorphism (auto)

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: rs1031381; hg19: chr11-134088682;