rs10505168

chr8-112643523-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198123.2(CSMD3):c.3310+1586A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 169,910 control chromosomes in the GnomAD database, including 11,265 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 0.35 (10179 hom., cov: 32)
  • Exomes 𝑓: 0.35 (1086 hom.)
• Consequence: CSMD3 NM_198123.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.470

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]

MIR2053 (HGNC:37069): (microRNA 2053) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSMD3	NM_198123.2	c.3310+1586A>G		intron_variant		ENST00000297405.10
MIR2053	NR_031745.1	n.31T>C		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSMD3	ENST00000297405.10	c.3310+1586A>G		intron_variant		1	NM_198123.2	P1
MIR2053	ENST00000459295.1	n.31T>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53610 AN: 151818 Hom.: 10169 Cov.: 32

Gnomad AFR AF: 0.500

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.316

GnomAD3 exomes AF: 0.330 AC: 7757 AN: 23476 Hom.: 1334 AF XY: 0.322 AC XY: 3374 AN XY: 10476

Gnomad AFR exome AF: 0.480

Gnomad AMR exome AF: 0.286

Gnomad ASJ exome AF: 0.254

Gnomad EAS exome AF: 0.448

Gnomad SAS exome AF: 0.269

Gnomad FIN exome AF: 0.354

Gnomad NFE exome AF: 0.283

Gnomad OTH exome AF: 0.261

GnomAD4 exome AF: 0.348 AC: 6251 AN: 17974 Hom.: 1086 Cov.: 0 AF XY: 0.343 AC XY: 2954 AN XY: 8604

Gnomad4 AFR exome AF: 0.446

Gnomad4 AMR exome AF: 0.167

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.289

Gnomad4 FIN exome AF: 0.358

Gnomad4 NFE exome AF: 0.308

Gnomad4 OTH exome AF: 0.353

GnomAD4 genome AF: 0.353 AC: 53662 AN: 151936 Hom.: 10179 Cov.: 32 AF XY: 0.357 AC XY: 26507 AN XY: 74274

Gnomad4 AFR AF: 0.499

Gnomad4 AMR AF: 0.316

Gnomad4 ASJ AF: 0.269

Gnomad4 EAS AF: 0.420

Gnomad4 SAS AF: 0.305

Gnomad4 FIN AF: 0.344

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.315

Alfa AF: 0.325 Hom.: 985

Bravo AF: 0.360

Asia WGS AF: 0.369 AC: 1282 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
Cadd	Benign	13
Dann	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs10505168; hg19: chr8-113655752; COSMIC: COSV52166930;