19-35269617-T-G

Position:

• chr19-35269617-T-G

Variant summary

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

The NM_003367.4(USF2):​c.146T>G​(p.Val49Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 0.00025 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: USF2 NM_003367.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.42

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USF2	NM_003367.4	c.146T>G	p.Val49Gly	missense_variant	3/10	ENST00000222305.8	NP_003358.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USF2	ENST00000222305.8	c.146T>G	p.Val49Gly	missense_variant	3/10	1	NM_003367.4	ENSP00000222305.2

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000245 AC: 352 AN: 1436668 Hom.: 0 Cov.: 33 AF XY: 0.000217 AC XY: 155 AN XY: 714382

Gnomad4 AFR exome AF: 0.000247

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.000157

Gnomad4 EAS exome AF: 0.0000259

Gnomad4 SAS exome AF: 0.000107

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000285

Gnomad4 OTH exome AF: 0.000271

GnomAD4 genome Cov.: 28

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

Apr 24, 2024

The c.146T>G (p.V49G) alteration is located in exon 3 (coding exon 3) of the USF2 gene. This alteration results from a T to G substitution at nucleotide position 146, causing the valine (V) at amino acid position 49 to be replaced by a glycine (G). 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	Uncertain	0.48
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	.;T;.;.;T
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.15
FATHMM_MKL	Benign	0.46	N
LIST_S2	Uncertain	0.93	D;D;D;D;D
M_CAP	Pathogenic	0.99	D
MetaRNN	Uncertain	0.50	T;T;T;T;T
MetaSVM	Uncertain	0.65	D
MutationAssessor	Uncertain	2.2	M;M;M;M;.
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-1.8	N;N;.;N;.
REVEL	Pathogenic	0.73
Sift	Benign	0.048	D;D;.;T;.
Sift4G	Uncertain	0.0030	D;D;D;T;D
Polyphen		0.97	D;P;.;.;P
Vest4		0.51
MutPred		0.43		.;.;.;.;Loss of sheet (P = 0.0104);
MVP		0.38
MPC		2.1
ClinPred		0.88	D
GERP RS		2.6
Varity_R		0.59
gMVP		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr19-35760520;