rs16826069

Variant names:

• chr1-39331383-A-C
• NM_001394062.1:c.4795A>C

Your query was ambiguous. Multiple possible variants found:

• chr1-39331383-A-C
• chr1-39331383-A-G
• chr1-39331383-A-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001394062.1(MACF1):​c.4795A>C​(p.Ile1599Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: MACF1 NM_001394062.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0980

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 Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.026988536).
• BS2: High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MACF1	NM_001394062.1	c.4795A>C	p.Ile1599Leu	missense_variant	Exon 37 of 101	ENST00000564288.6	NP_001380991.1
MACF1	NM_012090.5	c.4629+4030A>C		intron_variant	Intron 35 of 92		NP_036222.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MACF1	ENST00000564288.6	c.4795A>C	p.Ile1599Leu	missense_variant	Exon 37 of 101	5	NM_001394062.1	ENSP00000455274.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461838 Hom.: 0 Cov.: 49 AF XY: 0.00 AC XY: 0 AN XY: 727226

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: 0.00000540

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.049
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	13
DANN	Benign	0.67
DEOGEN2	Benign	0.031	T;T;T;.
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0075	N
LIST_S2	Benign	0.67	T;T;T;T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.027	T;T;T;T
MetaSVM	Benign	-0.96	T
PROVEAN	Benign	0.65	N;N;N;N
REVEL	Benign	0.13
Sift	Benign	1.0	T;T;T;T
Polyphen		0.0	.;B;.;.
Vest4		0.13
MutPred		0.64		.;Loss of helix (P = 0.079);.;.;
MVP		0.28
ClinPred		0.017	T
GERP RS		-7.8
Varity_R		0.023

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-39797055;