19-35269887-G-A

Position:

• chr19-35269887-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003367.4(USF2):​c.313G>A​(p.Ala105Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000797 in 1,255,316 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 8.0e-7 (0 hom.)
• Consequence: USF2 NM_003367.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.62

Genes affected

USF2 (HGNC:12594): (upstream transcription factor 2, c-fos interacting) This gene encodes a member of the basic helix-loop-helix leucine zipper family of transcription factors. The encoded protein can activate transcription through pyrimidine-rich initiator (Inr) elements and E-box motifs and is involved in regulating multiple cellular processes. [provided by RefSeq, Mar 2016]

USF2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23102826).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USF2	NM_003367.4	c.313G>A	p.Ala105Thr	missense_variant	4/10	ENST00000222305.8	NP_003358.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USF2	ENST00000222305.8	c.313G>A	p.Ala105Thr	missense_variant	4/10	1	NM_003367.4	ENSP00000222305.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.97e-7 AC: 1 AN: 1255316 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 611600

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000761

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 29, 2024

The c.313G>A (p.A105T) alteration is located in exon 4 (coding exon 4) of the USF2 gene. This alteration results from a G to A substitution at nucleotide position 313, causing the alanine (A) at amino acid position 105 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.067	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.062	T;.;T
Eigen	Benign	0.13
Eigen_PC	Benign	0.16
FATHMM_MKL	Benign	0.36	N
LIST_S2	Uncertain	0.92	D;D;D
M_CAP	Pathogenic	0.48	D
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Uncertain	0.23	D
MutationAssessor	Benign	1.3	L;L;.
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	0.23	N;.;.
REVEL	Uncertain	0.34
Sift	Benign	0.29	T;.;.
Sift4G	Benign	0.48	T;T;T
Polyphen		0.89	P;.;P
Vest4		0.23
MutPred		0.27		.;.;Loss of sheet (P = 0.0037);
MVP		0.37
MPC		1.1
ClinPred		0.79	D
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.094
gMVP		0.28

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-35760790;