Variant chr15-67208608-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_024666.5(AAGAB):c.669G>A(p.Arg223=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00125 in 1,614,130 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0016 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0012 ( 15 hom. )

Consequence

AAGAB
NM_024666.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0470

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 15-67208608-C-T is Benign according to our data. Variant chr15-67208608-C-T is described in ClinVar as [Benign]. Clinvar id is 769885.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.047 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00163 (248/152262) while in subpopulation EAS AF= 0.0347 (180/5194). AF 95% confidence interval is 0.0305. There are 3 homozygotes in gnomad4. There are 148 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 248 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
AAGAB	NM_024666.5 linkuse as main transcript	c.669G>A	p.Arg223=	synonymous_variant	7/10	ENST00000261880.10
AAGAB	NM_001271885.2 linkuse as main transcript	c.342G>A	p.Arg114=	synonymous_variant	7/10
AAGAB	NM_001271886.2 linkuse as main transcript	c.342G>A	p.Arg114=	synonymous_variant	7/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AAGAB	ENST00000261880.10 linkuse as main transcript	c.669G>A	p.Arg223=	synonymous_variant	7/10	1	NM_024666.5	P1	Q6PD74-1
AAGAB	ENST00000542650.5 linkuse as main transcript	c.342G>A	p.Arg114=	synonymous_variant	7/10	2			Q6PD74-2
AAGAB	ENST00000561452.5 linkuse as main transcript	c.342G>A	p.Arg114=	synonymous_variant	7/10	5			Q6PD74-2
AAGAB	ENST00000538028.1 linkuse as main transcript	n.350G>A		non_coding_transcript_exon_variant	4/7	2

Frequencies

GnomAD3 genomes

AF:

0.00162

AC:

247

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0344

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.00141

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00346

AC:

863

AN:

249552

Hom.:

AF XY:

0.00311

AC XY:

421

AN XY:

135388

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00492

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0318

Gnomad SAS exome

AF:

0.00105

Gnomad FIN exome

AF:

0.00227

Gnomad NFE exome

AF:

0.000230

Gnomad OTH exome

AF:

0.00231

GnomAD4 exome

AF:

0.00121

AC:

1769

AN:

1461868

Hom.:

Cov.:

AF XY:

0.00120

AC XY:

870

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.00434

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0278

Gnomad4 SAS exome

AF:

0.00102

Gnomad4 FIN exome

AF:

0.00217

Gnomad4 NFE exome

AF:

0.000119

Gnomad4 OTH exome

AF:

0.00217

GnomAD4 genome

AF:

0.00163

AC:

248

AN:

152262

Hom.:

Cov.:

AF XY:

0.00199

AC XY:

148

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0000963

Gnomad4 AMR

AF:

0.00151

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0347

Gnomad4 SAS

AF:

0.00311

Gnomad4 FIN

AF:

0.00141

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000300

Hom.:

Bravo

AF:

0.00159

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 18, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.98

DANN

Benign

0.40

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

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