NM_017832.4:c.69G>A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_017832.4(ABITRAM):c.69G>A(p.Trp23*) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000374 in 1,604,976 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

ABITRAM
NM_017832.4 stop_gained

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.69

Publications

1 publications found

Variant links:

Genes affected

ABITRAM (HGNC:1364): (actin binding transcription modulator) Predicted to enable actin filament binding activity and actin monomer binding activity. Predicted to be involved in dendrite morphogenesis; regulation of actin filament polymerization; and regulation of filopodium assembly. Predicted to be located in growth cone. Predicted to be active in several cellular components, including dendrite; filopodium tip; and lamellipodium. [provided by Alliance of Genome Resources, Apr 2022]

ABITRAM links:

ELP1 (HGNC:5959): (elongator acetyltransferase complex subunit 1) The protein encoded by this gene is a scaffold protein and a regulator for three different kinases involved in proinflammatory signaling. The encoded protein can bind NF-kappa-B-inducing kinase and I-kappa-B kinases through separate domains and assemble them into an active kinase complex. Mutations in this gene have been associated with familial dysautonomia. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2016]

ELP1 Gene-Disease associations (from GenCC):

primary dysautonomia
Inheritance: AR Classification: DEFINITIVE Submitted by: Myriad Women’s Health
Riley-Day syndrome
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
medulloblastoma
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ELP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017832.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABITRAM	NM_017832.4	MANE Select	c.69G>A	p.Trp23*	stop_gained	Exon 1 of 6	NP_060302.1	Q9NX38
	ABITRAM	NM_001410990.1		c.69G>A	p.Trp23*	stop_gained	Exon 1 of 4	NP_001397919.1	X6R8U7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ABITRAM	ENST00000322940.11	TSL:1 MANE Select	c.69G>A	p.Trp23*	stop_gained	Exon 1 of 6	ENSP00000363753.3	Q9NX38
ABITRAM	ENST00000964591.1		c.69G>A	p.Trp23*	stop_gained	Exon 1 of 7	ENSP00000634650.1
ABITRAM	ENST00000919245.1		c.69G>A	p.Trp23*	stop_gained	Exon 1 of 6	ENSP00000589304.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000856

AC:

AN:

233706

AF XY:

0.0000158

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000116

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000344

AC:

AN:

1452764

Hom.:

Cov.:

AF XY:

0.00000692

AC XY:

AN XY:

722180

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32308

American (AMR)

AF:

0.00

AC:

AN:

43982

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25806

East Asian (EAS)

AF:

0.000128

AC:

AN:

38970

South Asian (SAS)

AF:

0.00

AC:

AN:

84636

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52822

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5558

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1108672

Other (OTH)

AF:

0.00

AC:

AN:

60010

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41464

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000207

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Uncertain

0.058

BayesDel_noAF

Uncertain

0.070

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.053

Eigen

Pathogenic

0.95

Eigen_PC

Pathogenic

0.80

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.27

MetaRNN

Benign

0.38

MetaSVM

Benign

-0.71

PhyloP100

5.7

PROVEAN

Benign

-0.040

REVEL

Uncertain

0.35

Sift

Benign

0.12

Sift4G

Benign

0.30

MutPred

0.20

Loss of sheet (P = 0.0817)

MVP

0.96

ClinPred

0.95

GERP RS

4.5

PromoterAI

-0.0037

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=5/195

disease causing (fs/PTC)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over