rs1591593478

Variant names:

• chr12-8082371-A-C
• rs1591593478
• NM_015509.4:c.83A>C

Your query was ambiguous. Multiple possible variants found:

• chr12-8082371-A-C
• chr12-8082371-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015509.4(NECAP1):​c.83A>C​(p.Asn28Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. N28I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NECAP1 NM_015509.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.96

Genes affected

NECAP1 (HGNC:24539): (NECAP endocytosis associated 1) This gene encodes a protein containing two characteristic WXXF motifs. The encoded protein localizes to clathrin-coated vesicles, where it binds components of the adapter protein complexes and aids in endocytosis. Loss of function of this gene results in early infantile epileptic encephalopathy-21. There is a pseudogene for this gene on chromosome 7. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

ENSG00000284697 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40350038).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NECAP1	NM_015509.4	c.83A>C	p.Asn28Thr	missense_variant	Exon 1 of 8	ENST00000339754.11	NP_056324.2
NECAP1	NR_024260.2	n.98A>C		non_coding_transcript_exon_variant	Exon 1 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NECAP1	ENST00000339754.11	c.83A>C	p.Asn28Thr	missense_variant	Exon 1 of 8	1	NM_015509.4	ENSP00000341737.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.36
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T;T;.;.;.;.
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.97	.;D;D;D;D;D
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.40	T;T;T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.0	M;M;.;.;.;.
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-5.4	.;D;.;.;.;D
REVEL	Benign	0.29
Sift	Benign	0.062	.;T;.;.;.;T
Sift4G	Benign	0.15	.;T;.;.;.;T
Polyphen		0.53	P;P;.;.;.;.
Vest4		0.71
MutPred		0.45		Gain of catalytic residue at P24 (P = 2e-04);Gain of catalytic residue at P24 (P = 2e-04);Gain of catalytic residue at P24 (P = 2e-04);Gain of catalytic residue at P24 (P = 2e-04);Gain of catalytic residue at P24 (P = 2e-04);Gain of catalytic residue at P24 (P = 2e-04);
MVP		0.48
MPC		0.86
ClinPred		1.0	D
GERP RS		3.7
Varity_R		0.72
gMVP		0.60

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: rs1591593478; hg19: chr12-8234967;