chr1-39084253-G-T

Variant summary

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

The NM_012090.5(MACF1):​c.35G>T​(p.Arg12Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,536 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R12Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MACF1
NM_012090.5 missense

Scores

5
9
4

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.25
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MACF1NM_012090.5 linkc.35G>T p.Arg12Leu missense_variant Exon 1 of 93 NP_036222.3 Q9UPN3-2Q6ZSD7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MACF1ENST00000567887.5 linkc.35G>T p.Arg12Leu missense_variant Exon 1 of 101 5 ENSP00000455823.1 H3BQK9
MACF1ENST00000372915.8 linkc.35G>T p.Arg12Leu missense_variant Exon 1 of 96 5 ENSP00000362006.4 A0A7P0MQR8
MACF1ENST00000361689.7 linkc.35G>T p.Arg12Leu missense_variant Exon 2 of 94 5 ENSP00000354573.2 Q9UPN3-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251092
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135762
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460536
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
726652
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.58
BayesDel_addAF
Pathogenic
0.22
D
BayesDel_noAF
Uncertain
0.080
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.17
T;T;T;T;.
Eigen
Uncertain
0.57
Eigen_PC
Uncertain
0.62
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.93
.;D;D;D;D
M_CAP
Benign
0.052
D
MetaRNN
Uncertain
0.50
D;D;D;D;D
MetaSVM
Benign
-0.33
T
PrimateAI
Uncertain
0.76
T
PROVEAN
Pathogenic
-5.0
D;.;D;D;D
REVEL
Uncertain
0.35
Sift
Pathogenic
0.0
D;.;D;D;D
Sift4G
Uncertain
0.024
D;D;.;.;D
Vest4
0.58
MutPred
0.14
Loss of MoRF binding (P = 0.0419);Loss of MoRF binding (P = 0.0419);Loss of MoRF binding (P = 0.0419);Loss of MoRF binding (P = 0.0419);Loss of MoRF binding (P = 0.0419);
MVP
0.76
ClinPred
0.99
D
GERP RS
5.3
Varity_R
0.39
gMVP
0.59

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs200446050; hg19: chr1-39549925; COSMIC: COSV100486896; API