1-93534829-A-G

Variant names:

• chr1-93534829-A-G
• rs201882774
• NM_001164473.3:c.911A>G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001164473.3(FNBP1L):​c.911A>G​(p.Gln304Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000469 in 1,578,476 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 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000050 (0 hom.)
• Consequence: FNBP1L NM_001164473.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.73

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 Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.040242434).
• BS2: High AC in GnomAdExome4 at 71 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FNBP1L	NM_001164473.3	c.911A>G	p.Gln304Arg	missense_variant	Exon 9 of 17	ENST00000271234.13	NP_001157945.1
FNBP1L	NM_001024948.3	c.911A>G	p.Gln304Arg	missense_variant	Exon 9 of 14		NP_001020119.1
FNBP1L	NM_017737.5	c.911A>G	p.Gln304Arg	missense_variant	Exon 9 of 15		NP_060207.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FNBP1L	ENST00000271234.13	c.911A>G	p.Gln304Arg	missense_variant	Exon 9 of 17	5	NM_001164473.3	ENSP00000271234.7
FNBP1L	ENST00000260506.12	c.911A>G	p.Gln304Arg	missense_variant	Exon 9 of 14	1		ENSP00000260506.8
FNBP1L	ENST00000370253.6	c.911A>G	p.Gln304Arg	missense_variant	Exon 9 of 15	5		ENSP00000359275.2
FNBP1L	ENST00000424449.2	c.446A>G	p.Gln149Arg	missense_variant	Exon 4 of 12	2		ENSP00000397451.2

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152162 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000405 AC: 8 AN: 197582 Hom.: 0 AF XY: 0.0000571 AC XY: 6 AN XY: 105170

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000208

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: 0.0000237

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000498 AC: 71 AN: 1426314 Hom.: 0 Cov.: 31 AF XY: 0.0000538 AC XY: 38 AN XY: 705748

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000227

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000194

Gnomad4 NFE exome AF: 0.0000540

Gnomad4 OTH exome AF: 0.0000338

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152162 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74340

Gnomad4 AFR AF: 0.0000241

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: 0.0000594 Hom.: 0

Bravo AF: 0.0000907

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000122 AC: 1

ExAC AF: 0.0000416 AC: 5

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.911A>G (p.Q304R) alteration is located in exon 9 (coding exon 9) of the FNBP1L gene. This alteration results from a A to G substitution at nucleotide position 911, causing the glutamine (Q) at amino acid position 304 to be replaced by an arginine (R). 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	0.16
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	21
DANN	Benign	0.93
DEOGEN2	Benign	0.024	T;.;.;.
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.18
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.81	T;T;T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.040	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N;N;.;N
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.76	N;N;.;N
REVEL	Benign	0.058
Sift	Benign	0.44	T;T;.;T
Sift4G	Benign	0.56	T;T;T;T
Polyphen		0.55, 0.0	.;P;.;B
Vest4		0.23
MVP		0.37
MPC		0.55
ClinPred		0.099	T
GERP RS		4.2
Varity_R		0.084
gMVP		0.43

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: rs201882774; hg19: chr1-94000386;