Variant 1-39084311-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.0630

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]

MACF1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Protein	UniProt
MACF1	NM_012090.5 linkuse as main transcript	c.93G>A	p.Ser31=	synonymous_variant	1/93		NP_036222.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Protein	Appris	UniProt
MACF1	ENST00000567887.5 linkuse as main transcript	c.93G>A	p.Ser31=	synonymous_variant	1/101	5	ENSP00000455823
MACF1	ENST00000372915.8 linkuse as main transcript	c.93G>A	p.Ser31=	synonymous_variant	1/96	5	ENSP00000362006	P1
MACF1	ENST00000361689.7 linkuse as main transcript	c.93G>A	p.Ser31=	synonymous_variant	2/94	5	ENSP00000354573		Q9UPN3-2

Frequencies

GnomAD3 genomes

AF:

0.148

AC:

22569

AN:

152046

Hom.:

1971

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.174

AC XY:

126673

AN XY:

727080

show subpopulations

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.:

AF XY:

0.147

AC XY:

10954

AN XY:

74410

show subpopulations

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:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 10, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over