15-67208595-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_024666.5(AAGAB):c.682A>G(p.Asn228Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 1,614,174 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0057 ( 6 hom., cov: 33)

Exomes 𝑓: 0.00072 ( 15 hom. )

Consequence

AAGAB
NM_024666.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.439

Variant links:

Genes affected

AAGAB (HGNC:25662): (alpha and gamma adaptin binding protein) The protein encoded by this gene interacts with the gamma-adaptin and alpha-adaptin subunits of complexes involved in clathrin-coated vesicle trafficking. Mutations in this gene are associated with type I punctate palmoplantar keratoderma. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2012]

AAGAB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003647536).

BP6

Variant 15-67208595-T-C is Benign according to our data. Variant chr15-67208595-T-C is described in ClinVar as [Benign]. Clinvar id is 776916.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00567 (864/152324) while in subpopulation AFR AF= 0.0196 (816/41574). AF 95% confidence interval is 0.0185. There are 6 homozygotes in gnomad4. There are 402 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 864 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AAGAB	NM_024666.5 link	c.682A>G	p.Asn228Asp	missense_variant	Exon 7 of 10	ENST00000261880.10	NP_078942.3	Q6PD74-1
AAGAB	NM_001271885.2 link	c.355A>G	p.Asn119Asp	missense_variant	Exon 7 of 10		NP_001258814.1	Q6PD74-2
AAGAB	NM_001271886.2 link	c.355A>G	p.Asn119Asp	missense_variant	Exon 7 of 10		NP_001258815.1	Q6PD74-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
AAGAB	ENST00000261880.10 link	c.682A>G	p.Asn228Asp	missense_variant	Exon 7 of 10	1	NM_024666.5	ENSP00000261880.5	Q6PD74-1
AAGAB	ENST00000542650.5 link	c.355A>G	p.Asn119Asp	missense_variant	Exon 7 of 10	2		ENSP00000440735.1	Q6PD74-2
AAGAB	ENST00000561452.5 link	c.355A>G	p.Asn119Asp	missense_variant	Exon 7 of 10	5		ENSP00000453263.1	Q6PD74-2
AAGAB	ENST00000538028.1 link	n.363A>G		non_coding_transcript_exon_variant	Exon 4 of 7	2

Frequencies

GnomAD3 genomes

AF:

0.00565

AC:

860

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0195

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00223

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00140

AC:

350

AN:

249538

Hom.:

AF XY:

0.00108

AC XY:

146

AN XY:

135380

show subpopulations

Gnomad AFR exome

AF:

0.0196

Gnomad AMR exome

AF:

0.00101

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000795

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000717

AC:

1048

AN:

1461850

Hom.:

Cov.:

AF XY:

0.000638

AC XY:

464

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.0219

Gnomad4 AMR exome

AF:

0.00132

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000141

Gnomad4 OTH exome

AF:

0.00157

GnomAD4 genome

AF:

0.00567

AC:

864

AN:

152324

Hom.:

Cov.:

AF XY:

0.00540

AC XY:

402

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0196

Gnomad4 AMR

AF:

0.00222

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000987

Hom.:

Bravo

AF:

0.00648

ESP6500AA

AF:

0.0179

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00161

AC:

194

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 09, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.77

CADD

Benign

5.6

DANN

Benign

0.31

DEOGEN2

Benign

0.0012

T;.;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.038

LIST_S2

Benign

0.55

T;.;T

MetaRNN

Benign

0.0036

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.4

L;.;.

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.80

N;N;N

REVEL

Benign

0.037

Sift

Benign

0.64

T;T;T

Sift4G

Benign

0.87

T;T;T

Polyphen

0.053

B;.;.

Vest4

0.083

MVP

0.040

MPC

0.012

ClinPred

0.0060

GERP RS

0.33

Varity_R

0.047

gMVP

0.11

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

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