rs375940905

Variant names:

• chr1-57015051-C-A
• NM_001365792.1:c.1276G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-57015051-C-A
• chr1-57015051-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001365792.1(DAB1):​c.1276G>T​(p.Val426Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V426M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DAB1 NM_001365792.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.54

Genes affected

DAB1 (HGNC:2661): (DAB adaptor protein 1) The laminar organization of multiple neuronal types in the cerebral cortex is required for normal cognitive function. In mice, the disabled-1 gene plays a central role in brain development, directing the migration of cortical neurons past previously formed neurons to reach their proper layer. This gene is similar to disabled-1, and the protein encoded by this gene is thought to be a signal transducer that interacts with protein kinase pathways to regulate neuronal positioning in the developing brain. [provided by RefSeq, Jan 2017]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19433928).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAB1	NM_001365792.1	c.1276G>T	p.Val426Leu	missense_variant	Exon 12 of 15	ENST00000371236.7	NP_001352721.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAB1	ENST00000371236.7	c.1276G>T	p.Val426Leu	missense_variant	Exon 12 of 15	5	NM_001365792.1	ENSP00000360280.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461836 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727220

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.073	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.36	.;.;.;T
Eigen	Benign	0.11
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.86	.;D;D;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.19	T;T;T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.1	.;.;.;M
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.5	N;.;N;N
REVEL	Benign	0.081
Sift	Benign	0.13	T;.;T;T
Sift4G	Uncertain	0.049	D;D;T;D
Polyphen		0.15	B;B;P;P
Vest4		0.47
MutPred		0.18		.;.;.;Gain of glycosylation at P456 (P = 0.1094);
MVP		0.51
MPC		0.33
ClinPred		0.84	D
GERP RS		4.6
Varity_R		0.26
gMVP		0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr1-57480724;