chr10-102471332-G-A

Position:

chr10-102471332-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_024789.4(MFSD13A):c.764G>A(p.Arg255Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000726 in 1,613,762 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00045 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00075 ( 1 hom. )

Consequence

MFSD13A
NM_024789.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.78

Variant links:

Genes affected

MFSD13A (HGNC:26196): (major facilitator superfamily domain containing 13A) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

MFSD13A links:

LOC124902493 (HGNC:):

LOC124902493 links:

ACTR1A (HGNC:167): (actin related protein 1A) This gene encodes a 42.6 kD subunit of dynactin, a macromolecular complex consisting of 10-11 subunits ranging in size from 22 to 150 kD. Dynactin binds to both microtubules and cytoplasmic dynein. It is involved in a diverse array of cellular functions, including ER-to-Golgi transport, the centripetal movement of lysosomes and endosomes, spindle formation, chromosome movement, nuclear positioning, and axonogenesis. This subunit is present in 8-13 copies per dynactin molecule, and is the most abundant molecule in the dynactin complex. It is an actin-related protein, and is approximately 60% identical at the amino acid level to conventional actin. [provided by RefSeq, Jul 2008]

ACTR1A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06022671).

BP6

Variant 10-102471332-G-A is Benign according to our data. Variant chr10-102471332-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2252850.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MFSD13A	NM_024789.4 linkuse as main transcript	c.764G>A	p.Arg255Gln	missense_variant	6/10	ENST00000238936.8	NP_079065.2
LOC124902493	XR_007062270.1 linkuse as main transcript	n.81+1503C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MFSD13A	ENST00000238936.8 linkuse as main transcript	c.764G>A	p.Arg255Gln	missense_variant	6/10	5	NM_024789.4	ENSP00000238936	P1
MFSD13A	ENST00000369931.3 linkuse as main transcript	c.311G>A	p.Arg104Gln	missense_variant	5/6	1		ENSP00000358947
MFSD13A	ENST00000469294.1 linkuse as main transcript	n.152G>A		non_coding_transcript_exon_variant	2/3	3
ACTR1A	ENST00000636707.1 linkuse as main transcript	c.*138+1503C>T		intron_variant, NMD_transcript_variant		5		ENSP00000490634

Frequencies

GnomAD3 genomes

AF:

0.000447

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000867

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000306

AC:

AN:

251416

Hom.:

AF XY:

0.000302

AC XY:

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.000589

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000755

AC:

1103

AN:

1461560

Hom.:

Cov.:

AF XY:

0.000712

AC XY:

518

AN XY:

727060

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.000917

Gnomad4 OTH exome

AF:

0.00119

GnomAD4 genome

AF:

0.000447

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.000350

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000867

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000669

Hom.:

Bravo

AF:

0.000378

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.000329

AC:

EpiCase

AF:

0.000981

EpiControl

AF:

0.000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 06, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.23

T;.

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.72

T;T

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.060

T;T

MetaSVM

Benign

-0.73

MutationTaster

Benign

1.0

D;D;N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.22

N;N

REVEL

Uncertain

0.30

Sift

Benign

1.0

T;T

Sift4G

Benign

0.85

T;T

Polyphen

0.0

B;B

Vest4

0.031

MVP

0.76

MPC

0.21

ClinPred

0.062

GERP RS

4.4

Varity_R

0.036

gMVP

0.11

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