Variant 19-48015975-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_022142.5(ELSPBP1):c.291T>G(p.Ser97Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,750 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ELSPBP1
NM_022142.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.132

Variant links:

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]

ELSPBP1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.026642233).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELSPBP1	NM_022142.5 linkuse as main transcript	c.291T>G	p.Ser97Arg	missense_variant	4/7	ENST00000339841.7	NP_071425.3	Q96BH3A0A384NKL6
ELSPBP1	XM_017027130.2 linkuse as main transcript	c.426T>G	p.Ser142Arg	missense_variant	4/7		XP_016882619.1
ELSPBP1	XM_047439213.1 linkuse as main transcript	c.426T>G	p.Ser142Arg	missense_variant	4/6		XP_047295169.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ELSPBP1	ENST00000339841.7 linkuse as main transcript	c.291T>G	p.Ser97Arg	missense_variant	4/7	1	NM_022142.5	ENSP00000340660.2	Q96BH3
ELSPBP1	ENST00000593782.1 linkuse as main transcript	c.81T>G	p.Ser27Arg	missense_variant	1/4	5		ENSP00000472960.1	M0R331
ELSPBP1	ENST00000596043.5 linkuse as main transcript	c.153T>G	p.Ser51Arg	missense_variant	3/5	3		ENSP00000470903.1	M0R006
ELSPBP1	ENST00000597519.5 linkuse as main transcript	c.71-6195T>G		intron_variant		3		ENSP00000471690.1	M0R179

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251346

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135834

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461750

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727186

show subpopulations

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 10, 2023

The c.291T>G (p.S97R) alteration is located in exon 4 (coding exon 3) of the ELSPBP1 gene. This alteration results from a T to G substitution at nucleotide position 291, causing the serine (S) at amino acid position 97 to be replaced by an arginine (R). 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

0.11

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.66

DANN

Benign

0.099

DEOGEN2

Benign

0.0038

T;T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0035

LIST_S2

Benign

0.38

T;T;T

M_CAP

Benign

0.0013

MetaRNN

Benign

0.027

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-2.2

N;.;.

PrimateAI

Benign

0.34

PROVEAN

Benign

1.1

N;.;.

REVEL

Benign

0.048

Sift

Benign

0.81

T;.;.

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

B;.;.

Vest4

0.11

MutPred

0.47

Gain of MoRF binding (P = 0.1027);.;.;

MVP

0.16

MPC

0.14

ClinPred

0.034

GERP RS

2.5

Varity_R

0.047

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over