11-117428362-G-A

Position:

• chr11-117428362-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2 BP4_Moderate BS2

The NM_020693.4(DSCAML1):​c.6128C>T​(p.Ala2043Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000698 in 1,431,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 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: 0.0000070 (0 hom.)
• Consequence: DSCAML1 NM_020693.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.29

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 Likely_benign. Variant got -5 ACMG points.

• 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=0.11161101).
• BS2: High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSCAML1	NM_020693.4	c.6128C>T	p.Ala2043Val	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	c.6128C>T	p.Ala2043Val	missense_variant	33/33		NM_020693.4	ENSP00000498769
DSCAML1	ENST00000321322.6	c.6308C>T	p.Ala2103Val	missense_variant	33/33	1		ENSP00000315465	P1
DSCAML1	ENST00000651172.1	c.6308C>T	p.Ala2103Val	missense_variant	33/33			ENSP00000498407	P1
DSCAML1	ENST00000527706.5	c.5498C>T	p.Ala1833Val	missense_variant	31/31	5		ENSP00000434335

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000698 AC: 10 AN: 1431786 Hom.: 0 Cov.: 33 AF XY: 0.00000981 AC XY: 7 AN XY: 713382

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: 0.0000119

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000823

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 11, 2023

This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 2103 of the DSCAML1 protein (p.Ala2103Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DSCAML1-related conditions. ClinVar contains an entry for this variant (Variation ID: 2073478). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	23
DANN	Uncertain	0.99
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-0.96	T
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.90	N;N
REVEL	Benign	0.079
Sift	Benign	0.20	T;T
Sift4G	Benign	0.33	T;T
Vest4		0.17
MVP		0.33
MPC		0.0094
ClinPred		0.83	D
GERP RS		4.3
gMVP		0.23

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-117299078;