7-50445523-T-A

Variant names:

• chr7-50445523-T-A
• NM_001287492.4:c.1765A>T

Variant summary

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

The NM_001287492.4(FIGNL1):​c.1765A>T​(p.Ser589Cys) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: FIGNL1 NM_001287492.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.19

Genes affected

FIGNL1 (HGNC:13286): (fidgetin like 1) This gene encodes a member of the AAA ATPase family of proteins. The encoded protein is recruited to sites of DNA damage where it plays a role in DNA double-strand break repair via homologous recombination. This protein has also been shown to localize to the centrosome and inhibit ciliogenesis, and may regulate the proliferation and differentiation of osteoblasts. [provided by RefSeq, Oct 2016]

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=0.18560079).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FIGNL1	NM_001287492.4	c.1765A>T	p.Ser589Cys	missense_variant	Exon 4 of 4	ENST00000433017.6	NP_001274421.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FIGNL1	ENST00000433017.6	c.1765A>T	p.Ser589Cys	missense_variant	Exon 4 of 4	2	NM_001287492.4	ENSP00000399997.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1765A>T (p.S589C) alteration is located in exon 4 (coding exon 1) of the FIGNL1 gene. This alteration results from a A to T substitution at nucleotide position 1765, causing the serine (S) at amino acid position 589 to be replaced by a cysteine (C). 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	0.098
BayesDel_addAF	Uncertain	0.090	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	13
DANN	Benign	0.85
DEOGEN2	Benign	0.19	T;T;T;T;T;T;T;T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.74	.;.;.;T;.;.;.;.
M_CAP	Benign	0.076	D
MetaRNN	Benign	0.19	T;T;T;T;T;T;T;T
MetaSVM	Uncertain	0.34	D
MutationAssessor	Pathogenic	3.1	M;M;M;M;M;M;M;M
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-3.1	D;.;.;.;.;D;D;D
REVEL	Uncertain	0.32
Sift	Uncertain	0.0090	D;.;.;.;.;D;D;D
Sift4G	Uncertain	0.020	D;D;D;D;D;D;D;D
Polyphen		0.11	B;B;B;B;B;B;B;B
Vest4		0.24
MutPred		0.56		Loss of disorder (P = 0.0129);Loss of disorder (P = 0.0129);Loss of disorder (P = 0.0129);Loss of disorder (P = 0.0129);Loss of disorder (P = 0.0129);Loss of disorder (P = 0.0129);Loss of disorder (P = 0.0129);Loss of disorder (P = 0.0129);
MVP		0.69
MPC		0.021
ClinPred		0.27	T
GERP RS		3.7
Varity_R		0.28
gMVP		0.57

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: chr7-50513221;