19-48015969-A-C

Position:

• chr19-48015969-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022142.5(ELSPBP1):​c.285A>C​(p.Leu95Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 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)
• Consequence: ELSPBP1 NM_022142.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.85

Genes affected

ELSPBP1 (HGNC:14417): (epididymal sperm binding protein 1) The protein encoded by this gene belongs to the sperm-coating protein family of epididymal origin. This protein and its canine homolog are the first known examples of proteins with four tandemly arranged fibronectin type 2 (Fn2) domains in the Fn2-module protein family. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08822432).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELSPBP1	NM_022142.5	c.285A>C	p.Leu95Phe	missense_variant	4/7	ENST00000339841.7	NP_071425.3
ELSPBP1	XM_017027130.2	c.420A>C	p.Leu140Phe	missense_variant	4/7		XP_016882619.1
ELSPBP1	XM_047439213.1	c.420A>C	p.Leu140Phe	missense_variant	4/6		XP_047295169.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELSPBP1	ENST00000339841.7	c.285A>C	p.Leu95Phe	missense_variant	4/7	1	NM_022142.5	ENSP00000340660.2
ELSPBP1	ENST00000593782.1	c.75A>C	p.Leu25Phe	missense_variant	1/4	5		ENSP00000472960.1
ELSPBP1	ENST00000596043.5	c.147A>C	p.Leu49Phe	missense_variant	3/5	3		ENSP00000470903.1
ELSPBP1	ENST00000597519.5	c.71-6201A>C		intron_variant		3		ENSP00000471690.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Feb 28, 2024

The c.285A>C (p.L95F) alteration is located in exon 4 (coding exon 3) of the ELSPBP1 gene. This alteration results from a A to C substitution at nucleotide position 285, causing the leucine (L) at amino acid position 95 to be replaced by a phenylalanine (F). 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	Benign	0.061
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.021
DANN	Benign	0.16
DEOGEN2	Benign	0.0042	T;T;T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0021	N
LIST_S2	Benign	0.50	T;T;T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.088	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.12	N;.;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.56	N;.;.
REVEL	Benign	0.029
Sift	Benign	0.12	T;.;.
Sift4G	Benign	0.063	T;T;T
Polyphen		0.0020	B;.;.
Vest4		0.045
MutPred		0.61		Gain of catalytic residue at G96 (P = 0.3132);.;.;
MVP		0.088
MPC		0.14
ClinPred		0.21	T
GERP RS		-7.1
Varity_R		0.037

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: chr19-48519226;