rs150106545

Variant names:

• chr19-35872580-C-G
• NM_001024807.3:c.948C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-35872580-C-G
• chr19-35872580-C-T

Variant summary

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

The NM_001024807.3(APLP1):​c.948C>G​(p.Asp316Glu) 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 1,461,598 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D316D) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: APLP1 NM_001024807.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.315

Genes affected

APLP1 (HGNC:597): (amyloid beta precursor like protein 1) This gene encodes a member of the highly conserved amyloid precursor protein gene family. The encoded protein is a membrane-associated glycoprotein that is cleaved by secretases in a manner similar to amyloid beta A4 precursor protein cleavage. This cleavage liberates an intracellular cytoplasmic fragment that may act as a transcriptional activator. The encoded protein may also play a role in synaptic maturation during cortical development. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

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=0.11424747).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APLP1	NM_001024807.3	c.948C>G	p.Asp316Glu	missense_variant	Exon 7 of 17	ENST00000221891.9	NP_001019978.1
APLP1	NM_005166.5	c.948C>G	p.Asp316Glu	missense_variant	Exon 7 of 17		NP_005157.1
APLP1	XM_017026737.3	c.948C>G	p.Asp316Glu	missense_variant	Exon 7 of 16		XP_016882226.1
APLP1	XM_017026738.3	c.948C>G	p.Asp316Glu	missense_variant	Exon 7 of 16		XP_016882227.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APLP1	ENST00000221891.9	c.948C>G	p.Asp316Glu	missense_variant	Exon 7 of 17	1	NM_001024807.3	ENSP00000221891.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461598 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727104

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	16
DANN	Benign	0.80
DEOGEN2	Benign	0.0094	T;.;.;T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.69	D
LIST_S2	Uncertain	0.92	D;D;D;D
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.11	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	.;L;.;.
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	0.070	N;N;.;.
REVEL	Benign	0.040
Sift	Benign	0.42	T;T;.;.
Sift4G	Benign	0.80	T;T;T;T
Polyphen		0.041	B;P;B;.
Vest4		0.24
MutPred		0.20		.;Loss of MoRF binding (P = 0.1004);.;.;
MVP		0.57
MPC		1.1
ClinPred		0.68	D
GERP RS		-0.22
gMVP		0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr19-36363482;