1-39084311-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The ENST00000567887.5(MACF1):c.93G>A(p.Ser31=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 1,613,638 control chromosomes in the GnomAD database, including 25,821 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1971 hom., cov: 32)
  • Exomes 𝑓: 0.18 (23850 hom.)
• Consequence: MACF1 ENST00000567887.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0630

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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 1-39084311-G-A is Benign according to our data. Variant chr1-39084311-G-A is described in ClinVar as [Benign]. Clinvar id is 1258911.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.063 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MACF1	NM_012090.5	c.93G>A	p.Ser31=	synonymous_variant	1/93

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MACF1	ENST00000567887.5	c.93G>A	p.Ser31=	synonymous_variant	1/101	5
MACF1	ENST00000372915.8	c.93G>A	p.Ser31=	synonymous_variant	1/96	5		P1
MACF1	ENST00000361689.7	c.93G>A	p.Ser31=	synonymous_variant	2/94	5

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22569 AN: 152046 Hom.: 1971 Cov.: 32

Gnomad AFR AF: 0.0733

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.0567

Gnomad SAS AF: 0.0888

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.155

GnomAD3 exomes AF: 0.155 AC: 38867 AN: 251136 Hom.: 3470 AF XY: 0.158 AC XY: 21456 AN XY: 135796

Gnomad AFR exome AF: 0.0665

Gnomad AMR exome AF: 0.0903

Gnomad ASJ exome AF: 0.269

Gnomad EAS exome AF: 0.0616

Gnomad SAS exome AF: 0.101

Gnomad FIN exome AF: 0.232

Gnomad NFE exome AF: 0.191

Gnomad OTH exome AF: 0.171

GnomAD4 exome AF: 0.175 AC: 256050 AN: 1461476 Hom.: 23850 Cov.: 33 AF XY: 0.174 AC XY: 126673 AN XY: 727080

Gnomad4 AFR exome AF: 0.0640

Gnomad4 AMR exome AF: 0.0962

Gnomad4 ASJ exome AF: 0.261

Gnomad4 EAS exome AF: 0.0693

Gnomad4 SAS exome AF: 0.103

Gnomad4 FIN exome AF: 0.223

Gnomad4 NFE exome AF: 0.188

Gnomad4 OTH exome AF: 0.164

GnomAD4 genome AF: 0.148 AC: 22580 AN: 152162 Hom.: 1971 Cov.: 32 AF XY: 0.147 AC XY: 10954 AN XY: 74410

Gnomad4 AFR AF: 0.0734

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.273

Gnomad4 EAS AF: 0.0572

Gnomad4 SAS AF: 0.0883

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.189

Gnomad4 OTH AF: 0.154

Alfa AF: 0.168 Hom.: 2166

Bravo AF: 0.140

Asia WGS AF: 0.0570 AC: 197 AN: 3478

EpiCase AF: 0.194

EpiControl AF: 0.196

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 10, 2019	- -

Lissencephaly 9 with complex brainstem malformation Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Apr 11, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
Cadd	Benign	9.9
Dann	Benign	0.89

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: rs3736890; hg19: chr1-39549983; COSMIC: COSV58378498;