rs534976924

Variant names:

• chr1-93536351-C-A
• rs534976924
• NM_001164473.3:c.1010C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-93536351-C-A
• chr1-93536351-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001164473.3(FNBP1L):​c.1010C>A​(p.Thr337Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000431 in 1,390,520 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T337I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: FNBP1L NM_001164473.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.06

Genes affected

FNBP1L (HGNC:20851): (formin binding protein 1 like) The protein encoded by this gene binds to both CDC42 and N-WASP. This protein promotes CDC42-induced actin polymerization by activating the N-WASP-WIP complex and, therefore, is involved in a pathway that links cell surface signals to the actin cytoskeleton. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.19391847).
• BS2: High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FNBP1L	NM_001164473.3	c.1010C>A	p.Thr337Asn	missense_variant	Exon 10 of 17	ENST00000271234.13	NP_001157945.1
FNBP1L	NM_001024948.3	c.990+1443C>A		intron_variant	Intron 9 of 13		NP_001020119.1
FNBP1L	NM_017737.5	c.990+1443C>A		intron_variant	Intron 9 of 14		NP_060207.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FNBP1L	ENST00000271234.13	c.1010C>A	p.Thr337Asn	missense_variant	Exon 10 of 17	5	NM_001164473.3	ENSP00000271234.7
FNBP1L	ENST00000260506.12	c.990+1443C>A		intron_variant	Intron 9 of 13	1		ENSP00000260506.8
FNBP1L	ENST00000424449.2	c.545C>A	p.Thr182Asn	missense_variant	Exon 5 of 12	2		ENSP00000397451.2
FNBP1L	ENST00000370253.6	c.990+1443C>A		intron_variant	Intron 9 of 14	5		ENSP00000359275.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000130 AC: 2 AN: 153366 Hom.: 0 AF XY: 0.0000123 AC XY: 1 AN XY: 81278

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: 0.0000332

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000431 AC: 6 AN: 1390520 Hom.: 0 Cov.: 30 AF XY: 0.00000146 AC XY: 1 AN XY: 686064

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: 0.00000558

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	22
DANN	Benign	0.95
DEOGEN2	Benign	0.027	T;.
Eigen	Benign	-0.050
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.34	N;.
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.52	N;.
REVEL	Benign	0.12
Sift	Benign	0.37	T;.
Sift4G	Benign	0.33	T;T
Vest4		0.30
MVP		0.52
MPC		0.51
ClinPred		0.20	T
GERP RS		5.2
Varity_R		0.15
gMVP		0.30

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

Other links and lift over

dbSNP: rs534976924; hg19: chr1-94001908;