rs221533

Variant names:

• chr6-99308715-C-T
• rs221533
• NM_032511.4:c.823+14729G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032511.4(FAXC):​c.823+14729G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.876 in 152,084 control chromosomes in the GnomAD database, including 58,752 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.88 (58752 hom., cov: 31)
• Consequence: FAXC NM_032511.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.180
• Publications: 3 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAXC	NM_032511.4	c.823+14729G>A		intron_variant	Intron 4 of 5	ENST00000389677.6	NP_115900.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAXC	ENST00000389677.6	c.823+14729G>A		intron_variant	Intron 4 of 5	1	NM_032511.4	ENSP00000374328.4
FAXC	ENST00000538471.1	c.-17-16895G>A		intron_variant	Intron 1 of 2	1		ENSP00000445267.1

Frequencies

GnomAD3 genomes AF: 0.875 AC: 133032 AN: 151966 Hom.: 58691 Cov.: 31

Gnomad AFR AF: 0.970

Gnomad AMI AF: 0.843

Gnomad AMR AF: 0.845

Gnomad ASJ AF: 0.923

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.973

Gnomad FIN AF: 0.765

Gnomad MID AF: 0.959

Gnomad NFE AF: 0.822

Gnomad OTH AF: 0.889

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.876 AC: 133153 AN: 152084 Hom.: 58752 Cov.: 31 AF XY: 0.874 AC XY: 64987 AN XY: 74332

African (AFR) AF: 0.970 AC: 40295 AN: 41542

American (AMR) AF: 0.845 AC: 12914 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.923 AC: 3206 AN: 3472

East Asian (EAS) AF: 0.998 AC: 5177 AN: 5186

South Asian (SAS) AF: 0.973 AC: 4696 AN: 4824

European-Finnish (FIN) AF: 0.765 AC: 8036 AN: 10502

Middle Eastern (MID) AF: 0.956 AC: 281 AN: 294

European-Non Finnish (NFE) AF: 0.822 AC: 55897 AN: 67966

Other (OTH) AF: 0.891 AC: 1884 AN: 2114

Alfa AF: 0.837 Hom.: 6682

Bravo AF: 0.883

Asia WGS AF: 0.979 AC: 3397 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	6.8
DANN	Benign	0.58
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs221533; hg19: chr6-99756591;