19-35269887-G-T

Variant names:

• chr19-35269887-G-T
• rs1023619519
• NM_003367.4:c.313G>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_003367.4(USF2):​c.313G>T​(p.Ala105Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000568 in 1,407,420 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A105T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000056 (0 hom.)
• Consequence: USF2 NM_003367.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.62
• Publications: 0 publications found

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]

ENSG00000307673 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.21164149).
• BS2: High AC in GnomAdExome4 at 7 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003367.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USF2	NM_003367.4	MANE Select	c.313G>T	p.Ala105Ser	missense	Exon 4 of 10	NP_003358.1	Q15853-1
	USF2	NM_207291.3		c.228+188G>T		intron	N/A	NP_997174.1	Q15853-3
	USF2	NM_001321150.2		c.228+188G>T		intron	N/A	NP_001308079.1	Q15853-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USF2	ENST00000222305.8	TSL:1 MANE Select	c.313G>T	p.Ala105Ser	missense	Exon 4 of 10	ENSP00000222305.2	Q15853-1
	USF2	ENST00000343550.9	TSL:1	c.228+188G>T		intron	N/A	ENSP00000340633.4	Q15853-3
	USF2	ENST00000379134.7	TSL:1	c.228+188G>T		intron	N/A	ENSP00000368429.3	Q15853-4

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152094 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000132 AC: 2 AN: 15156 AF XY: 0.000119

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: 0.000315

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00236

GnomAD4 exome AF: 0.00000558 AC: 7 AN: 1255326 Hom.: 0 Cov.: 34 AF XY: 0.00000491 AC XY: 3 AN XY: 611602

African (AFR) AF: 0.00 AC: 0 AN: 24206

American (AMR) AF: 0.00 AC: 0 AN: 13142

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17870

East Asian (EAS) AF: 0.00 AC: 0 AN: 28222

South Asian (SAS) AF: 0.00 AC: 0 AN: 58284

European-Finnish (FIN) AF: 0.0000277 AC: 1 AN: 36142

Middle Eastern (MID) AF: 0.000986 AC: 4 AN: 4056

European-Non Finnish (NFE) AF: 9.79e-7 AC: 1 AN: 1021608

Other (OTH) AF: 0.0000193 AC: 1 AN: 51796

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152094 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74294

African (AFR) AF: 0.00 AC: 0 AN: 41420

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67996

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000948 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.073	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Benign	0.15
Eigen_PC	Benign	0.17
FATHMM_MKL	Benign	0.53	D
LIST_S2	Uncertain	0.89	D
M_CAP	Pathogenic	0.52	D
MetaRNN	Benign	0.21	T
MetaSVM	Uncertain	0.18	D
MutationAssessor	Benign	1.8	L
PhyloP100		4.6
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-0.19	N
REVEL	Uncertain	0.37
Sift	Benign	0.061	T
Sift4G	Benign	0.34	T
Polyphen		0.95	P
Vest4		0.28
MutPred		0.28		Loss of sheet (P = 0.0104)
MVP		0.44
MPC		1.6
ClinPred		0.12	T
GERP RS		3.2
PromoterAI		0.0010	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.21
Mutation Taster		=69/31	polymorphism

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: rs1023619519; hg19: chr19-35760790;