rs757882940

Variant names:

• chr3-194138115-G-A
• rs757882940
• NM_005524.4:c.725G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-194138115-G-A
• chr3-194138115-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005524.4(HES1):​c.725G>A​(p.Gly242Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. G242A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: HES1 NM_005524.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.11
• Publications: 1 publications found

Genes affected

HES1 (HGNC:5192): (hes family bHLH transcription factor 1) This protein belongs to the basic helix-loop-helix family of transcription factors. It is a transcriptional repressor of genes that require a bHLH protein for their transcription. The protein has a particular type of basic domain that contains a helix interrupting protein that binds to the N-box rather than the canonical E-box. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HES1	NM_005524.4	c.725G>A	p.Gly242Asp	missense_variant	Exon 4 of 4	ENST00000232424.4	NP_005515.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HES1	ENST00000232424.4	c.725G>A	p.Gly242Asp	missense_variant	Exon 4 of 4	1	NM_005524.4	ENSP00000232424.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.64
BayesDel_addAF	Uncertain	0.020	T
BayesDel_noAF	Benign	-0.21
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.87	D
M_CAP	Uncertain	0.098	D
MetaRNN	Uncertain	0.69	D
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	1.5	L
PhyloP100		5.1
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.24
Sift	Benign	0.038	D
Sift4G	Benign	0.21	T
Polyphen		0.99	D
Vest4		0.62
MutPred		0.47		Loss of glycosylation at S241 (P = 0.0416);
MVP		0.57
MPC		1.6
ClinPred		0.91	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.21
gMVP		0.70
Mutation Taster		=51/49	polymorphism

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

Other links and lift over

dbSNP: rs757882940; hg19: chr3-193855904; COSMIC: COSV51685571; COSMIC: COSV51685571;