6-118907511-A-G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_014034.3(ASF1A):c.512A>G(p.Gln171Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000013 in 1,613,508 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

ASF1A
NM_014034.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.15

Publications

0 publications found

Variant links:

Genes affected

ASF1A (HGNC:20995): (anti-silencing function 1A histone chaperone) This gene encodes a member of the H3/H4 family of histone chaperone proteins and is similar to the anti-silencing function-1 gene in yeast. The protein is a key component of a histone donor complex that functions in nucleosome assembly. It interacts with histones H3 and H4, and functions together with a chromatin assembly factor during DNA replication and repair. [provided by RefSeq, Jul 2008]

ASF1A links:

MCM9 (HGNC:21484): (minichromosome maintenance 9 homologous recombination repair factor) The protein encoded by this gene is a member of the mini-chromosome maintenance (MCM) protein family that are essential for the initiation of eukaryotic genome replication. Binding of this protein to chromatin has been shown to be a pre-requisite for recruiting the MCM2-7 helicase to DNA replication origins. This protein also binds, and is a positive regulator of, the chromatin licensing and DNA replication factor 1, CDT1. [provided by RefSeq, Nov 2010]

MCM9 Gene-Disease associations (from GenCC):

premature ovarian failure 10
Inheritance: AR, AD Classification: DEFINITIVE, LIMITED Submitted by: Ambry Genetics
46,XX ovarian dysgenesis-short stature syndrome
Inheritance: AR, Unknown Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
male infertility
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

MCM9 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12731564).

BS2

High AC in GnomAdExome4 at 20 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014034.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ASF1A	NM_014034.3	MANE Select	c.512A>G	p.Gln171Arg	missense	Exon 4 of 4	NP_054753.1	Q9Y294
MCM9	NM_017696.3	MANE Select	c.1150+4139T>C		intron	N/A	NP_060166.2
MCM9	NM_001378356.1		c.1150+4139T>C		intron	N/A	NP_001365285.1	Q9NXL9-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ASF1A	ENST00000229595.6	TSL:1 MANE Select	c.512A>G	p.Gln171Arg	missense	Exon 4 of 4	ENSP00000229595.5	Q9Y294
MCM9	ENST00000619706.5	TSL:5 MANE Select	c.1150+4139T>C		intron	N/A	ENSP00000480469.1	Q9NXL9-1
ASF1A	ENST00000877924.1		c.476A>G	p.Gln159Arg	missense	Exon 4 of 4	ENSP00000547983.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000281

AC:

AN:

248878

AF XY:

0.0000222

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000870

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.0000137

AC:

AN:

1461304

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

726936

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33460

American (AMR)

AF:

0.0000671

AC:

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39644

South Asian (SAS)

AF:

0.00

AC:

AN:

86244

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53394

Middle Eastern (MID)

AF:

0.00174

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1111620

Other (OTH)

AF:

0.0000497

AC:

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41468

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.21

Eigen

Benign

-0.22

Eigen_PC

Benign

0.021

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.74

M_CAP

Benign

0.0027

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

PhyloP100

4.2

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.96

REVEL

Benign

0.063

Sift

Benign

0.48

Sift4G

Benign

0.44

Polyphen

0.0040

Vest4

0.27

MutPred

0.15

Gain of phosphorylation at S172 (P = 0.0936)

MVP

0.23

MPC

0.92

ClinPred

0.089

GERP RS

4.8

Varity_R

0.12

gMVP

0.74

Mutation Taster

=80/20

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over