14-44504992-C-A

Variant names:

• chr14-44504992-C-A
• rs1566598128
• NM_032135.4:c.1996G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032135.4(FSCB):​c.1996G>T​(p.Ala666Ser) 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. 16/22 in silico tools predict 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. A666T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 21)
• Consequence: FSCB NM_032135.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00700
• Publications: 0 publications found

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]

LINC02277 (HGNC:53193): (long intergenic non-protein coding RNA 2277)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11530408).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032135.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FSCB	NM_032135.4	MANE Select	c.1996G>T	p.Ala666Ser	missense	Exon 1 of 1	NP_115511.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FSCB	ENST00000340446.5	TSL:6 MANE Select	c.1996G>T	p.Ala666Ser	missense	Exon 1 of 1	ENSP00000344579.4	Q5H9T9
	LINC02277	ENST00000557721.2	TSL:2	n.108-60170G>T		intron	N/A
	LINC02277	ENST00000795526.1		n.108-60170G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome Cov.: 40

GnomAD4 genome Cov.: 21

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.21
DANN	Benign	0.92
DEOGEN2	Benign	0.0020	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.094	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		-0.0070
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.047
Sift	Benign	0.46	T
Sift4G	Benign	0.24	T
Polyphen		0.99	D
Vest4		0.066
MutPred		0.25		Gain of phosphorylation at A666 (P = 0.002)
MVP		0.12
MPC		0.013
ClinPred		0.21	T
GERP RS		2.6
Varity_R		0.028
gMVP		0.034
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs1566598128; hg19: chr14-44974195;