19-35270769-A-C

Position:

• chr19-35270769-A-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_003367.4(USF2):​c.632A>C​(p.Gln211Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000616 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: USF2 NM_003367.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.96

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.20659217).
• BS2: High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USF2	NM_003367.4	c.632A>C	p.Gln211Pro	missense_variant	6/10	ENST00000222305.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USF2	ENST00000222305.8	c.632A>C	p.Gln211Pro	missense_variant	6/10	1	NM_003367.4	P3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000199 AC: 5 AN: 251420 Hom.: 0 AF XY: 0.0000221 AC XY: 3 AN XY: 135888

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000272

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461864 Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4 AN XY: 727234

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000202

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	21
DANN	Uncertain	0.98
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.051
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.95	D;D;D;D;D;D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.21	T;T;T;T;T;T;T
MetaSVM	Uncertain	0.053	D
MutationTaster	Benign	0.98	D;D;D
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-2.3	N;N;.;N;.;.;.
REVEL	Benign	0.22
Sift	Benign	0.21	T;T;.;D;.;.;.
Sift4G	Benign	0.41	T;T;T;T;T;T;T
Polyphen		0.0070	B;B;B;.;B;.;.
Vest4		0.39
MutPred		0.31		.;.;.;.;Gain of glycosylation at T206 (P = 0.0513);.;.;
MVP		0.44
MPC		1.0
ClinPred		0.15	T
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.31
gMVP		0.68

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: rs766640758; hg19: chr19-35761672;