ENST00000567887.5:c.83G>A

Variant names:

• chr1-39084301-G-A
• rs775020443
• ENST00000567887.5:c.83G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000567887.5(MACF1):​c.83G>A​(p.Ser28Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S28T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MACF1 ENST00000567887.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.05

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2607183).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MACF1	NM_012090.5	c.83G>A	p.Ser28Asn	missense_variant	Exon 1 of 93		NP_036222.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MACF1	ENST00000567887.5	c.83G>A	p.Ser28Asn	missense_variant	Exon 1 of 101	5		ENSP00000455823.1
MACF1	ENST00000372915.8	c.83G>A	p.Ser28Asn	missense_variant	Exon 1 of 96	5		ENSP00000362006.4
MACF1	ENST00000361689.7	c.83G>A	p.Ser28Asn	missense_variant	Exon 2 of 94	5		ENSP00000354573.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251264 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135846

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T;T;T;T;.
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.82	.;T;T;T;T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.26	T;T;T;T;T
MetaSVM	Benign	-0.43	T
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-2.4	N;.;N;N;N
REVEL	Benign	0.18
Sift	Pathogenic	0.0	D;.;D;D;D
Sift4G	Uncertain	0.026	D;D;.;.;D
Vest4		0.48
MutPred		0.072		Loss of phosphorylation at S28 (P = 8e-04);Loss of phosphorylation at S28 (P = 8e-04);Loss of phosphorylation at S28 (P = 8e-04);Loss of phosphorylation at S28 (P = 8e-04);Loss of phosphorylation at S28 (P = 8e-04);
MVP		0.55
ClinPred		0.96	D
GERP RS		5.3
Varity_R		0.40
gMVP		0.45

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

Other links and lift over

dbSNP: rs775020443; hg19: chr1-39549973;