NM_001164473.3:c.163C>G

Variant names:

• chr1-93522104-C-G
• rs991512677
• NM_001164473.3:c.163C>G

Variant summary

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

The NM_001164473.3(FNBP1L):​c.163C>G​(p.Pro55Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000729 in 1,371,238 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: FNBP1L NM_001164473.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.61
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164473.3. 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
	FNBP1L	NM_001164473.3	MANE Select	c.163C>G	p.Pro55Ala	missense	Exon 3 of 17	NP_001157945.1	Q5T0N5-1
	FNBP1L	NM_001024948.3		c.163C>G	p.Pro55Ala	missense	Exon 3 of 14	NP_001020119.1	Q5T0N5-4
	FNBP1L	NM_017737.5		c.163C>G	p.Pro55Ala	missense	Exon 3 of 15	NP_060207.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FNBP1L	ENST00000271234.13	TSL:5 MANE Select	c.163C>G	p.Pro55Ala	missense	Exon 3 of 17	ENSP00000271234.7	Q5T0N5-1
	FNBP1L	ENST00000260506.12	TSL:1	c.163C>G	p.Pro55Ala	missense	Exon 3 of 14	ENSP00000260506.8	Q5T0N5-4
	FNBP1L	ENST00000868905.1		c.163C>G	p.Pro55Ala	missense	Exon 3 of 16	ENSP00000538964.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.29e-7 AC: 1 AN: 1371238 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 678750

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 29924

American (AMR) AF: 0.00 AC: 0 AN: 35608

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23806

East Asian (EAS) AF: 0.00 AC: 0 AN: 35676

South Asian (SAS) AF: 0.00 AC: 0 AN: 68930

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49778

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4716

European-Non Finnish (NFE) AF: 9.38e-7 AC: 1 AN: 1066646

Other (OTH) AF: 0.00 AC: 0 AN: 56154

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

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
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.044	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.040	D
MetaRNN	Uncertain	0.50	D
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	1.9	L
PhyloP100		6.6
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-5.0	D
REVEL	Benign	0.22
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.025	D
Polyphen		1.0	D
Vest4		0.57
MutPred		0.56		Loss of glycosylation at P55 (P = 0.0075)
MVP		0.43
MPC		0.94
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.57
gMVP		0.29
Mutation Taster		=45/55	disease causing

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: rs991512677; hg19: chr1-93987661;