ENST00000567887.5:c.59_76delGTCGGAGTGAGCGATCTT

Variant names:

• chr1-39084272-GTCTTGTCGGAGTGAGCGA-G
• rs751392944
• ENST00000567887.5:c.59_76delGTCGGAGTGAGCGATCTT

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM4 BS2

The ENST00000567887.5(MACF1):​c.59_76delGTCGGAGTGAGCGATCTT​(p.Cys20_Ser25del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.0000109 in 1,461,332 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: MACF1 ENST00000567887.5 disruptive_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.85

Genes affected

MACF1 (HGNC:13664): (microtubule actin crosslinking factor 1) This gene encodes a large protein containing numerous spectrin and leucine-rich repeat (LRR) domains. The encoded protein is a member of a family of proteins that form bridges between different cytoskeletal elements. This protein facilitates actin-microtubule interactions at the cell periphery and couples the microtubule network to cellular junctions. Alternative splicing results in multiple transcript variants, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, May 2013]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in ENST00000567887.5.
• BS2: High AC in GnomAdExome4 at 16 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MACF1	NM_012090.5	c.59_76delGTCGGAGTGAGCGATCTT	p.Cys20_Ser25del	disruptive_inframe_deletion	Exon 1 of 93		NP_036222.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MACF1	ENST00000567887.5	c.59_76delGTCGGAGTGAGCGATCTT	p.Cys20_Ser25del	disruptive_inframe_deletion	Exon 1 of 101	5		ENSP00000455823.1
MACF1	ENST00000372915.8	c.59_76delGTCGGAGTGAGCGATCTT	p.Cys20_Ser25del	disruptive_inframe_deletion	Exon 1 of 96	5		ENSP00000362006.4
MACF1	ENST00000361689.7	c.59_76delGTCGGAGTGAGCGATCTT	p.Cys20_Ser25del	disruptive_inframe_deletion	Exon 2 of 94	5		ENSP00000354573.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000159 AC: 4 AN: 251248 Hom.: 0 AF XY: 0.0000147 AC XY: 2 AN XY: 135828

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000109 AC: 16 AN: 1461332 Hom.: 0 AF XY: 0.00000963 AC XY: 7 AN XY: 727002

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000108

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

May 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MACF1: PM4 -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs751392944; hg19: chr1-39549944;