Genetic Variant FAXC:p.Ser395Thr (chr6-99281211-A-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_032511.4(FAXC):c.1183T>A(p.Ser395Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000104 in 1,440,300 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

FAXC
NM_032511.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.95

Publications

0 publications found

Variant links:

Genes affected

FAXC (HGNC:20742): (failed axon connections homolog, metaxin like GST domain containing) Predicted to be integral component of membrane. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

FAXC links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.34165865).

BS2

High AC in GnomAdExome4 at 15 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032511.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAXC	NM_032511.4	MANE Select	c.1183T>A	p.Ser395Thr	missense	Exon 6 of 6	NP_115900.1	Q5TGI0-1
FAXC	NM_001346531.2		c.1024T>A	p.Ser342Thr	missense	Exon 7 of 7	NP_001333460.1
FAXC	NM_001346532.1		c.1024T>A	p.Ser342Thr	missense	Exon 7 of 7	NP_001333461.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAXC	ENST00000389677.6	TSL:1 MANE Select	c.1183T>A	p.Ser395Thr	missense	Exon 6 of 6	ENSP00000374328.4	Q5TGI0-1
FAXC	ENST00000538471.1	TSL:1	c.343T>A	p.Ser115Thr	missense	Exon 3 of 3	ENSP00000445267.1	Q5TGI0-2
FAXC	ENST00000461803.1	TSL:2	n.350T>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251372

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000104

AC:

AN:

1440300

Hom.:

Cov.:

AF XY:

0.0000111

AC XY:

AN XY:

718034

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33042

American (AMR)

AF:

0.00

AC:

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25972

East Asian (EAS)

AF:

0.00

AC:

AN:

39556

South Asian (SAS)

AF:

0.00

AC:

AN:

85834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5728

European-Non Finnish (NFE)

AF:

0.0000128

AC:

AN:

1092346

Other (OTH)

AF:

0.0000167

AC:

AN:

59714

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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

Cov.:

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.00000378

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

0.32

BayesDel_addAF

Uncertain

0.049

BayesDel_noAF

Benign

-0.17

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.057

Eigen

Pathogenic

0.71

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.012

MetaRNN

Benign

0.34

MetaSVM

Benign

-0.38

MutationAssessor

Uncertain

2.0

PhyloP100

8.9

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.75

REVEL

Benign

0.25

Sift

Uncertain

0.0090

Sift4G

Pathogenic

0.0

Polyphen

0.97

Vest4

0.52

MutPred

0.17

Loss of stability (P = 0.0085)

MVP

0.21

MPC

1.1

ClinPred

0.85

GERP RS

5.1

Varity_R

0.24

gMVP

0.48

Mutation Taster

=51/49

polymorphism

(source)

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

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