Variant 11-117428440-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_020693.4(DSCAML1):c.6050A>G(p.His2017Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DSCAML1
NM_020693.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.31

Variant links:

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]

DSCAML1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), DSCAML1. . Gene score misZ 3.15 (greater than the threshold 3.09). Trascript score misZ 4.5764 (greater than threshold 3.09). GenCC has associacion of gene with motor neuron disorder, retinal disorder.

BP4

Computational evidence support a benign effect (MetaRNN=0.15894598).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSCAML1	NM_020693.4 linkuse as main transcript	c.6050A>G	p.His2017Arg	missense_variant	33/33	ENST00000651296.2	NP_065744.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSCAML1	ENST00000651296.2 linkuse as main transcript	c.6050A>G	p.His2017Arg	missense_variant	33/33		NM_020693.4	ENSP00000498769		Q8TD84-1
DSCAML1	ENST00000321322.6 linkuse as main transcript	c.6230A>G	p.His2077Arg	missense_variant	33/33	1		ENSP00000315465	P1
DSCAML1	ENST00000651172.1 linkuse as main transcript	c.6230A>G	p.His2077Arg	missense_variant	33/33			ENSP00000498407	P1
DSCAML1	ENST00000527706.5 linkuse as main transcript	c.5420A>G	p.His1807Arg	missense_variant	31/31	5		ENSP00000434335		Q8TD84-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000521

AC:

AN:

192006

Hom.:

AF XY:

0.00000953

AC XY:

AN XY:

104924

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000108

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1389240

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

685464

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 02, 2023

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with DSCAML1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.001%). This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 2077 of the DSCAML1 protein (p.His2077Arg). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.057

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Benign

0.95

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.18

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.73

T;T

M_CAP

Benign

0.046

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-0.89

MutationTaster

Benign

0.79

D;D

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-1.0

N;N

REVEL

Benign

0.086

Sift

Benign

0.17

T;T

Sift4G

Benign

0.24

T;T

Vest4

0.31

MVP

0.57

MPC

0.0088

ClinPred

0.19

GERP RS

4.8

gMVP

0.30

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over