1-77916044-AT-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_144573.4(NEXN):c.-52-4del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000463 in 1,102,328 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000037 (0 hom.)
• Consequence: NEXN NM_144573.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.282

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 1-77916044-AT-A is Benign according to our data. Variant chr1-77916044-AT-A is described in ClinVar as [Likely_benign]. Clinvar id is 518082.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 16 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEXN	NM_144573.4	c.-52-4del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000334785.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEXN	ENST00000334785.12	c.-52-4del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_144573.4	P3
NEXN	ENST00000401035.7	c.-52-4del		splice_polypyrimidine_tract_variant, intron_variant		1
NEXN	ENST00000330010.12	c.-52-4del		splice_polypyrimidine_tract_variant, intron_variant		2		A1
NEXN	ENST00000440324.5	c.-52-4del		splice_polypyrimidine_tract_variant, intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.000105 AC: 16 AN: 151976 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000368 AC: 35 AN: 950352 Hom.: 0 Cov.: 12 AF XY: 0.0000379 AC XY: 18 AN XY: 475094

Gnomad4 AFR exome AF: 0.000458

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000594

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000933

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000225

Gnomad4 OTH exome AF: 0.000129

GnomAD4 genome AF: 0.000105 AC: 16 AN: 151976 Hom.: 0 Cov.: 33 AF XY: 0.000175 AC XY: 13 AN XY: 74236

Gnomad4 AFR AF: 0.000362

Gnomad4 AMR AF: 0.0000655

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.000110

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs972673849; hg19: chr1-78381729;