chr7-50445764-TTGAGA-T

Variant names:

• chr7-50445764-TTGAGA-T
• rs535171403
• NM_001287492.4:c.1519_1523delTCTCA

Variant summary

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

The NM_001287492.4(FIGNL1):​c.1519_1523delTCTCA​(p.Ser507ThrfsTer5) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000682 in 1,614,108 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00043 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00071 (0 hom.)
• Consequence: FIGNL1 NM_001287492.4 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.13
• Publications: 1 publications found

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

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001287492.4. 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
	FIGNL1	NM_001287492.4	MANE Select	c.1519_1523delTCTCA	p.Ser507ThrfsTer5	frameshift	Exon 4 of 4	NP_001274421.1	Q6PIW4-1
	FIGNL1	NM_001042762.5		c.1519_1523delTCTCA	p.Ser507ThrfsTer5	frameshift	Exon 4 of 4	NP_001036227.1	Q6PIW4-1
	FIGNL1	NM_001287493.3		c.1519_1523delTCTCA	p.Ser507ThrfsTer5	frameshift	Exon 3 of 3	NP_001274422.1	Q6PIW4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FIGNL1	ENST00000433017.6	TSL:2 MANE Select	c.1519_1523delTCTCA	p.Ser507ThrfsTer5	frameshift	Exon 4 of 4	ENSP00000399997.1	Q6PIW4-1
	FIGNL1	ENST00000356889.8	TSL:1	c.1519_1523delTCTCA	p.Ser507ThrfsTer5	frameshift	Exon 4 of 4	ENSP00000349356.4	Q6PIW4-1
	FIGNL1	ENST00000419119.1	TSL:1	c.1519_1523delTCTCA	p.Ser507ThrfsTer5	frameshift	Exon 2 of 2	ENSP00000410811.1	Q6PIW4-1

Frequencies

GnomAD3 genomes AF: 0.000427 AC: 65 AN: 152242 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000896

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000366 AC: 92 AN: 251354 AF XY: 0.000397

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000616

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.000709 AC: 1036 AN: 1461866 Hom.: 0 AF XY: 0.000682 AC XY: 496 AN XY: 727230

African (AFR) AF: 0.0000896 AC: 3 AN: 33480

American (AMR) AF: 0.000134 AC: 6 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000301 AC: 26 AN: 86258

European-Finnish (FIN) AF: 0.0000562 AC: 3 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000849 AC: 944 AN: 1112002

Other (OTH) AF: 0.000894 AC: 54 AN: 60396

GnomAD4 genome AF: 0.000427 AC: 65 AN: 152242 Hom.: 0 Cov.: 33 AF XY: 0.000336 AC XY: 25 AN XY: 74376

African (AFR) AF: 0.0000241 AC: 1 AN: 41462

American (AMR) AF: 0.000131 AC: 2 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5206

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000896 AC: 61 AN: 68046

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000648 Hom.: 0

Bravo AF: 0.000389

EpiCase AF: 0.00104

EpiControl AF: 0.000771

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.1
Mutation Taster		=8/192	disease causing

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs535171403; hg19: chr7-50513462;