Genetic Variant NM_144573.4:c.-53+141G>T (chr1-77888900-G-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_144573.4(NEXN):c.-53+141G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 152,428 control chromosomes in the GnomAD database, including 6,204 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6195 hom., cov: 32)

Exomes 𝑓: 0.20 ( 9 hom. )

Consequence

NEXN
NM_144573.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.467

Publications

3 publications found

Variant links:

Genes affected

NEXN (HGNC:29557): (nexilin F-actin binding protein) This gene encodes a filamentous actin-binding protein that may function in cell adhesion and migration. Mutations in this gene have been associated with dilated cardiomyopathy, also known as CMD1CC. Alternatively spliced transcript variants have been described.[provided by RefSeq, Feb 2010]

NEXN links:

NEXN-AS1 (HGNC:31983): (NEXN antisense RNA 1)

NEXN-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 1-77888900-G-T is Benign according to our data. Variant chr1-77888900-G-T is described in ClinVar as [Benign]. Clinvar id is 1233836.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEXN	NM_144573.4 link	c.-53+141G>T		intron_variant	Intron 1 of 12	ENST00000334785.12	NP_653174.3	Q0ZGT2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEXN	ENST00000334785.12 link	c.-53+141G>T		intron_variant	Intron 1 of 12	1	NM_144573.4	ENSP00000333938.7		Q0ZGT2-1

Frequencies

GnomAD3 genomes

AF:

0.277

AC:

42167

AN:

151978

Hom.:

6192

Cov.:

show subpopulations

Gnomad AFR

AF:

0.364

Gnomad AMI

AF:

0.260

Gnomad AMR

AF:

0.200

Gnomad ASJ

AF:

0.271

Gnomad EAS

AF:

0.395

Gnomad SAS

AF:

0.187

Gnomad FIN

AF:

0.201

Gnomad MID

AF:

0.253

Gnomad NFE

AF:

0.253

Gnomad OTH

AF:

0.255

GnomAD4 exome

AF:

0.200

AC:

AN:

330

Hom.:

Cov.:

AF XY:

0.198

AC XY:

AN XY:

258

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.375

AC:

AN:

South Asian (SAS)

AF:

0.214

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.250

AC:

AN:

European-Non Finnish (NFE)

AF:

0.199

AC:

AN:

276

Other (OTH)

AF:

0.167

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.277

AC:

42184

AN:

152098

Hom.:

6195

Cov.:

AF XY:

0.271

AC XY:

20166

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.364

AC:

15110

AN:

41518

American (AMR)

AF:

0.200

AC:

3060

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.271

AC:

940

AN:

3472

East Asian (EAS)

AF:

0.395

AC:

2033

AN:

5146

South Asian (SAS)

AF:

0.188

AC:

908

AN:

4826

European-Finnish (FIN)

AF:

0.201

AC:

2134

AN:

10614

Middle Eastern (MID)

AF:

0.241

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.253

AC:

17159

AN:

67904

Other (OTH)

AF:

0.252

AC:

532

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1571

3142

4714

6285

7856

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.283

Hom.:

912

Bravo

AF:

0.285

Asia WGS

AF:

0.262

AC:

907

AN:

3474

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

- -

Jun 23, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.98

(source)

DANN

Benign

0.52

PhyloP100

-0.47

PromoterAI

-0.054

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(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

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NM_144573.4:c.-53+141G>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over