Variant 14-44504955-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032135.4(FSCB):c.2033C>A(p.Ala678Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000499 in 1,604,576 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

FSCB
NM_032135.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.233

Variant links:

Genes affected

FSCB (HGNC:20494): (fibrous sheath CABYR binding protein) Predicted to enable calcium ion binding activity. Predicted to be involved in negative regulation of protein sumoylation. Predicted to be active in sperm fibrous sheath and sperm principal piece. [provided by Alliance of Genome Resources, Apr 2022]

FSCB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.107840985).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FSCB	NM_032135.4 linkuse as main transcript	c.2033C>A	p.Ala678Asp	missense_variant	1/1	ENST00000340446.5	NP_115511.3	Q5H9T9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FSCB	ENST00000340446.5 linkuse as main transcript	c.2033C>A	p.Ala678Asp	missense_variant	1/1	6	NM_032135.4	ENSP00000344579.4		Q5H9T9

Frequencies

GnomAD3 genomes

AF:

0.00000670

AC:

AN:

149308

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000412

AC:

AN:

1455160

Hom.:

Cov.:

AF XY:

0.00000829

AC XY:

AN XY:

723868

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:

0.00000541

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000134

AC:

AN:

149416

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

73142

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000378

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

Oct 29, 2024

The c.2033C>A (p.A678D) alteration is located in exon 1 (coding exon 1) of the FSCB gene. This alteration results from a C to A substitution at nucleotide position 2033, causing the alanine (A) at amino acid position 678 to be replaced by an aspartic acid (D). 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

0.19

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

8.9

DANN

Benign

0.92

DEOGEN2

Benign

0.061

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.090

LIST_S2

Benign

0.65

M_CAP

Benign

0.0086

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.058

Sift

Benign

0.18

Sift4G

Uncertain

0.017

Polyphen

0.99

Vest4

0.17

MutPred

0.19

Loss of helix (P = 0.028);

MVP

0.15

MPC

0.014

ClinPred

0.60

GERP RS

-1.9

Varity_R

0.11

gMVP

0.077

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