8-113305443-C-T

Variant names:

• chr8-113305443-C-T
• rs7012271
• NM_198123.2:c.401+9128G>A

Variant summary

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

The NM_198123.2(CSMD3):​c.401+9128G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.629 in 152,004 control chromosomes in the GnomAD database, including 30,980 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 0.63 (30980 hom., cov: 33)
• Consequence: CSMD3 NM_198123.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.161
• Publications: 3 publications found

Genes affected

CSMD3 (HGNC:19291): (CUB and Sushi multiple domains 3) Predicted to be involved in regulation of dendrite development. Predicted to be located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

CSMD3 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198123.2. 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
	CSMD3	NM_198123.2	MANE Select	c.401+9128G>A		intron	N/A	NP_937756.1	Q7Z407-1
	CSMD3	NM_198124.2		c.281+9128G>A		intron	N/A	NP_937757.1	Q7Z407-2
	CSMD3	NM_052900.3		c.401+9128G>A		intron	N/A	NP_443132.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSMD3	ENST00000297405.10	TSL:1 MANE Select	c.401+9128G>A		intron	N/A	ENSP00000297405.5	Q7Z407-1
	CSMD3	ENST00000343508.7	TSL:1	c.281+9128G>A		intron	N/A	ENSP00000345799.3	Q7Z407-2
	CSMD3	ENST00000455883.2	TSL:1	c.401+9128G>A		intron	N/A	ENSP00000412263.2	Q7Z407-3

Frequencies

GnomAD3 genomes AF: 0.629 AC: 95609 AN: 151886 Hom.: 30974 Cov.: 33

Gnomad AFR AF: 0.465

Gnomad AMI AF: 0.688

Gnomad AMR AF: 0.721

Gnomad ASJ AF: 0.640

Gnomad EAS AF: 0.745

Gnomad SAS AF: 0.678

Gnomad FIN AF: 0.676

Gnomad MID AF: 0.685

Gnomad NFE AF: 0.688

Gnomad OTH AF: 0.619

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

GnomAD4 genome AF: 0.629 AC: 95641 AN: 152004 Hom.: 30980 Cov.: 33 AF XY: 0.630 AC XY: 46857 AN XY: 74318

African (AFR) AF: 0.464 AC: 19226 AN: 41424

American (AMR) AF: 0.722 AC: 11026 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.640 AC: 2219 AN: 3468

East Asian (EAS) AF: 0.745 AC: 3852 AN: 5170

South Asian (SAS) AF: 0.680 AC: 3280 AN: 4824

European-Finnish (FIN) AF: 0.676 AC: 7131 AN: 10552

Middle Eastern (MID) AF: 0.671 AC: 196 AN: 292

European-Non Finnish (NFE) AF: 0.688 AC: 46787 AN: 67980

Other (OTH) AF: 0.618 AC: 1301 AN: 2106

Alfa AF: 0.643 Hom.: 6873

Bravo AF: 0.627

Asia WGS AF: 0.667 AC: 2312 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.5
DANN	Benign	0.68
PhyloP100		0.16
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: rs7012271; hg19: chr8-114317672;