chr1-42227926-A-G

Position:

• chr1-42227926-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014947.5(FOXJ3):​c.485T>C​(p.Val162Ala) variant causes a missense change. The variant allele was found at a frequency of 0.792 in 1,572,792 control chromosomes in the GnomAD database, including 494,393 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.79 (47901 hom., cov: 31)
  • Exomes 𝑓: 0.79 (446492 hom.)
• Consequence: FOXJ3 NM_014947.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.91

Genes affected

FOXJ3 (HGNC:29178): (forkhead box J3) Enables DNA-binding transcription activator activity, RNA polymerase II-specific and sequence-specific double-stranded DNA binding activity. Involved in positive regulation of transcription by RNA polymerase II. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.146454E-6).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.839 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXJ3	NM_014947.5	c.485T>C	p.Val162Ala	missense_variant	5/13	ENST00000361346.6	NP_055762.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXJ3	ENST00000361346.6	c.485T>C	p.Val162Ala	missense_variant	5/13	1	NM_014947.5	ENSP00000354620.1

Frequencies

GnomAD3 genomes AF: 0.793 AC: 120508 AN: 152032 Hom.: 47856 Cov.: 31

Gnomad AFR AF: 0.764

Gnomad AMI AF: 0.729

Gnomad AMR AF: 0.851

Gnomad ASJ AF: 0.855

Gnomad EAS AF: 0.826

Gnomad SAS AF: 0.748

Gnomad FIN AF: 0.823

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.789

Gnomad OTH AF: 0.826

GnomAD3 exomes AF: 0.808 AC: 201386 AN: 249164 Hom.: 81844 AF XY: 0.804 AC XY: 108321 AN XY: 134784

Gnomad AFR exome AF: 0.763

Gnomad AMR exome AF: 0.910

Gnomad ASJ exome AF: 0.851

Gnomad EAS exome AF: 0.826

Gnomad SAS exome AF: 0.739

Gnomad FIN exome AF: 0.817

Gnomad NFE exome AF: 0.795

Gnomad OTH exome AF: 0.806

GnomAD4 exome AF: 0.792 AC: 1124670 AN: 1420642 Hom.: 446492 Cov.: 34 AF XY: 0.790 AC XY: 557614 AN XY: 705750

Gnomad4 AFR exome AF: 0.764

Gnomad4 AMR exome AF: 0.904

Gnomad4 ASJ exome AF: 0.846

Gnomad4 EAS exome AF: 0.807

Gnomad4 SAS exome AF: 0.740

Gnomad4 FIN exome AF: 0.813

Gnomad4 NFE exome AF: 0.788

Gnomad4 OTH exome AF: 0.799

GnomAD4 genome AF: 0.793 AC: 120612 AN: 152150 Hom.: 47901 Cov.: 31 AF XY: 0.793 AC XY: 59001 AN XY: 74376

Gnomad4 AFR AF: 0.764

Gnomad4 AMR AF: 0.851

Gnomad4 ASJ AF: 0.855

Gnomad4 EAS AF: 0.825

Gnomad4 SAS AF: 0.749

Gnomad4 FIN AF: 0.823

Gnomad4 NFE AF: 0.789

Gnomad4 OTH AF: 0.825

Alfa AF: 0.796 Hom.: 120231

Bravo AF: 0.797

TwinsUK AF: 0.787 AC: 2919

ALSPAC AF: 0.784 AC: 3023

ESP6500AA AF: 0.767 AC: 3378

ESP6500EA AF: 0.790 AC: 6797

ExAC AF: 0.803 AC: 97530

Asia WGS AF: 0.741 AC: 2579 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.047
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	16
DANN	Benign	0.92
DEOGEN2	Benign	0.054	T;T;T;.;T;.
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.048	.;.;.;T;T;T
MetaRNN	Benign	0.0000011	T;T;T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.60	N;N;N;N;N;.
PrimateAI	Benign	0.43	T
PROVEAN	Benign	0.27	N;N;N;N;N;N
REVEL	Benign	0.23
Sift	Benign	1.0	T;T;T;T;T;T
Sift4G	Benign	0.53	T;T;T;T;T;T
Polyphen		0.0	B;B;B;B;B;.
Vest4		0.029
MPC		0.31
ClinPred		0.0056	T
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.028
gMVP		0.57

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

Other links and lift over

dbSNP: rs343376; hg19: chr1-42693597; COSMIC: COSV62360386;