rs773900197

Variant names:

• chr8-94641998-G-A
• NM_017697.4:c.175G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-94641998-G-A
• chr8-94641998-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_017697.4(ESRP1):​c.175G>A​(p.Glu59Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,644 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. E59Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ESRP1 NM_017697.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.92

Genes affected

ESRP1 (HGNC:25966): (epithelial splicing regulatory protein 1) ESPR1 is an epithelial cell-type-specific splicing regulator (Warzecha et al., 2009 [PubMed 19285943]).[supplied by OMIM, Aug 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39803058).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESRP1	NM_017697.4	c.175G>A	p.Glu59Lys	missense_variant	Exon 2 of 16	ENST00000433389.8	NP_060167.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ESRP1	ENST00000433389.8	c.175G>A	p.Glu59Lys	missense_variant	Exon 2 of 16	1	NM_017697.4	ENSP00000405738.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461644 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727108

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.35
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.062	.;T;T;.;.;.
Eigen	Benign	0.095
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.98	D;.;D;D;D;D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.40	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;L;L;L;L;.
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-2.2	N;N;.;N;.;N
REVEL	Benign	0.099
Sift	Benign	0.24	T;T;.;T;.;T
Sift4G	Benign	0.49	T;T;.;T;.;T
Polyphen		0.0020, 0.0060	.;B;B;B;B;.
Vest4		0.34
MutPred		0.48		Gain of methylation at E59 (P = 0.0105);Gain of methylation at E59 (P = 0.0105);Gain of methylation at E59 (P = 0.0105);Gain of methylation at E59 (P = 0.0105);Gain of methylation at E59 (P = 0.0105);Gain of methylation at E59 (P = 0.0105);
MVP		0.20
MPC		0.65
ClinPred		0.97	D
GERP RS		4.8
Varity_R		0.43
gMVP		0.35

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: chr8-95654226;