dbSNP rs1171096378: ASF1A:p.Glu29Asp (chr6-118894500-G-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014034.3(ASF1A):c.87G>C(p.Glu29Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000144 in 1,384,796 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ASF1A
NM_014034.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.08

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASF1A	NM_014034.3 link	c.87G>C	p.Glu29Asp	missense_variant	Exon 1 of 4	ENST00000229595.6	NP_054753.1	Q9Y294
MCM9	NM_017696.3 link	c.1150+17150C>G		intron_variant	Intron 8 of 13	ENST00000619706.5	NP_060166.2	Q9NXL9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASF1A	ENST00000229595.6 link	c.87G>C	p.Glu29Asp	missense_variant	Exon 1 of 4	1	NM_014034.3	ENSP00000229595.5		Q9Y294
MCM9	ENST00000619706.5 link	c.1150+17150C>G		intron_variant	Intron 8 of 13	5	NM_017696.3	ENSP00000480469.1		Q9NXL9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000705

AC:

AN:

141894

Hom.:

AF XY:

0.0000132

AC XY:

AN XY:

75888

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000171

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000144

AC:

AN:

1384796

Hom.:

Cov.:

AF XY:

0.00000146

AC XY:

AN XY:

683350

show subpopulations

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:

0.00000185

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.88

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Uncertain

0.0

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.47

Eigen

Benign

-0.042

Eigen_PC

Benign

0.083

FATHMM_MKL

Uncertain

0.83

LIST_S2

Pathogenic

0.97

M_CAP

Benign

0.030

MetaRNN

Uncertain

0.57

MetaSVM

Benign

-0.87

MutationAssessor

Uncertain

2.6

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-2.2

REVEL

Uncertain

0.52

Sift

Benign

0.048

Sift4G

Uncertain

0.056

Polyphen

0.015

Vest4

0.66

MutPred

0.76

Gain of helix (P = 0.132);

MVP

0.27

MPC

0.83

ClinPred

0.68

GERP RS

4.1

Varity_R

0.68

gMVP

0.70

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over