11-117428323-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_020693.4(DSCAML1):c.*5C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 1,479,982 control chromosomes in the GnomAD database, including 75,392 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.36 (11287 hom., cov: 31)
  • Exomes 𝑓: 0.30 (64105 hom.)
• Consequence: DSCAML1 NM_020693.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.95

Genes affected

DSCAML1 (HGNC:14656): (DS cell adhesion molecule like 1) The protein encoded by this gene is a member of the Ig superfamily of cell adhesion molecules and is involved in neuronal differentiation. The encoded membrane-bound protein localizes to the cell surface, where it forms aggregates that repel neuronal processes of the same cell type. [provided by RefSeq, Sep 2016]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 11-117428323-G-C is Benign according to our data. Variant chr11-117428323-G-C is described in ClinVar as [Benign]. Clinvar id is 3060836.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DSCAML1	NM_020693.4	c.*5C>G		3_prime_UTR_variant	33/33	ENST00000651296.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DSCAML1	ENST00000651296.2	c.*5C>G		3_prime_UTR_variant	33/33		NM_020693.4
DSCAML1	ENST00000321322.6	c.*5C>G		3_prime_UTR_variant	33/33	1		P1
DSCAML1	ENST00000527706.5	c.*5C>G		3_prime_UTR_variant	31/31	5
DSCAML1	ENST00000651172.1			downstream_gene_variant				P1

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54191 AN: 151276 Hom.: 11275 Cov.: 31

Gnomad AFR AF: 0.574

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.0474

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.260

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.332

GnomAD3 exomes AF: 0.290 AC: 65844 AN: 227044 Hom.: 11279 AF XY: 0.296 AC XY: 36963 AN XY: 125066

Gnomad AFR exome AF: 0.571

Gnomad AMR exome AF: 0.165

Gnomad ASJ exome AF: 0.324

Gnomad EAS exome AF: 0.0428

Gnomad SAS exome AF: 0.411

Gnomad FIN exome AF: 0.288

Gnomad NFE exome AF: 0.291

Gnomad OTH exome AF: 0.292

GnomAD4 exome AF: 0.301 AC: 399748 AN: 1328590 Hom.: 64105 Cov.: 22 AF XY: 0.303 AC XY: 201974 AN XY: 666398

Gnomad4 AFR exome AF: 0.583

Gnomad4 AMR exome AF: 0.180

Gnomad4 ASJ exome AF: 0.325

Gnomad4 EAS exome AF: 0.0446

Gnomad4 SAS exome AF: 0.410

Gnomad4 FIN exome AF: 0.288

Gnomad4 NFE exome AF: 0.298

Gnomad4 OTH exome AF: 0.307

GnomAD4 genome AF: 0.358 AC: 54233 AN: 151392 Hom.: 11287 Cov.: 31 AF XY: 0.355 AC XY: 26301 AN XY: 74004

Gnomad4 AFR AF: 0.574

Gnomad4 AMR AF: 0.249

Gnomad4 ASJ AF: 0.323

Gnomad4 EAS AF: 0.0475

Gnomad4 SAS AF: 0.417

Gnomad4 FIN AF: 0.291

Gnomad4 NFE AF: 0.288

Gnomad4 OTH AF: 0.328

Alfa AF: 0.247 Hom.: 1251

Bravo AF: 0.358

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

DSCAML1-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.0060
Dann	Benign	0.55

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: rs3741283; hg19: chr11-117299039; COSMIC: COSV58384855;