11-134152936-G-A

Variant names:

• chr11-134152936-G-A
• rs200642279
• NM_015261.3:c.*8C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS1

The NM_015261.3(NCAPD3):​c.*8C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000711 in 1,532,560 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000043 (0 hom.)
• Consequence: NCAPD3 NM_015261.3 3_prime_UTR
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.202
• Publications: 0 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 11-134152936-G-A is Benign according to our data. Variant chr11-134152936-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3354212.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000328 (50/152318) while in subpopulation AFR AF = 0.00106 (44/41572). AF 95% confidence interval is 0.000809. There are 0 homozygotes in GnomAd4. There are 27 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015261.3. 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
	NCAPD3	NM_015261.3	MANE Select	c.*8C>T		3_prime_UTR	Exon 35 of 35	NP_056076.1	P42695
	NCAPD3	NM_001372068.1		c.*8C>T		3_prime_UTR	Exon 35 of 35	NP_001358997.1	A0A8I5KT00
	NCAPD3	NM_001372069.1		c.*8C>T		3_prime_UTR	Exon 34 of 34	NP_001358998.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCAPD3	ENST00000534548.7	TSL:1 MANE Select	c.*8C>T		3_prime_UTR	Exon 35 of 35	ENSP00000433681.3	P42695
	NCAPD3	ENST00000525964.7	TSL:1	n.*2147C>T		non_coding_transcript_exon	Exon 36 of 36	ENSP00000431612.2	E9PKK4
	NCAPD3	ENST00000525964.7	TSL:1	n.*2147C>T		3_prime_UTR	Exon 36 of 36	ENSP00000431612.2	E9PKK4

Frequencies

GnomAD3 genomes AF: 0.000322 AC: 49 AN: 152200 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000126 AC: 24 AN: 191190 AF XY: 0.0000994

Gnomad AFR exome AF: 0.00122

Gnomad AMR exome AF: 0.0000811

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000607

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000110

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000427 AC: 59 AN: 1380242 Hom.: 0 Cov.: 30 AF XY: 0.0000354 AC XY: 24 AN XY: 677986

African (AFR) AF: 0.00127 AC: 39 AN: 30776

American (AMR) AF: 0.0000900 AC: 3 AN: 33334

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21000

East Asian (EAS) AF: 0.0000256 AC: 1 AN: 39024

South Asian (SAS) AF: 0.0000416 AC: 3 AN: 72082

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50640

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4600

European-Non Finnish (NFE) AF: 0.00000560 AC: 6 AN: 1071944

Other (OTH) AF: 0.000123 AC: 7 AN: 56842

GnomAD4 genome AF: 0.000328 AC: 50 AN: 152318 Hom.: 0 Cov.: 33 AF XY: 0.000363 AC XY: 27 AN XY: 74462

African (AFR) AF: 0.00106 AC: 44 AN: 41572

American (AMR) AF: 0.000196 AC: 3 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000427 Hom.: 0

Bravo AF: 0.000321

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	NCAPD3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.72
DANN	Benign	0.65
PhyloP100		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs200642279; hg19: chr11-134022831;