NM_005892.4:c.52C>T

Variant names:

• chr17-45222176-C-T
• rs1001732920
• NM_005892.4:c.52C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_005892.4(FMNL1):​c.52C>T​(p.Pro18Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000163 in 1,226,546 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 9.3e-7 (0 hom.)
• Consequence: FMNL1 NM_005892.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0790
• Publications: 0 publications found

Genes affected

FMNL1 (HGNC:1212): (formin like 1) This gene encodes a formin-related protein. Formin-related proteins have been implicated in morphogenesis, cytokinesis, and cell polarity. An alternative splice variant has been described but its full length sequence has not been determined. [provided by RefSeq, Jul 2008]

FMNL1-DT (HGNC:55311): (FMNL1 divergent transcript)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14130628).
• BP6: Variant 17-45222176-C-T is Benign according to our data. Variant chr17-45222176-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2262615.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005892.4. 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
	FMNL1	NM_005892.4	MANE Select	c.52C>T	p.Pro18Ser	missense	Exon 1 of 27	NP_005883.3
	FMNL1	NM_001411128.1		c.52C>T	p.Pro18Ser	missense	Exon 1 of 26	NP_001398057.1	O95466-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FMNL1	ENST00000331495.8	TSL:1 MANE Select	c.52C>T	p.Pro18Ser	missense	Exon 1 of 27	ENSP00000329219.2	O95466-1
	FMNL1	ENST00000587489.6	TSL:1	c.52C>T	p.Pro18Ser	missense	Exon 1 of 26	ENSP00000465474.2	K7EK60
	FMNL1	ENST00000947279.1		c.52C>T	p.Pro18Ser	missense	Exon 2 of 28	ENSP00000617338.1

Frequencies

GnomAD3 genomes AF: 0.00000664 AC: 1 AN: 150526 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.000484

GnomAD4 exome AF: 9.29e-7 AC: 1 AN: 1076020 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 518642

African (AFR) AF: 0.00 AC: 0 AN: 21274

American (AMR) AF: 0.00 AC: 0 AN: 8124

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12758

East Asian (EAS) AF: 0.00 AC: 0 AN: 21950

South Asian (SAS) AF: 0.00 AC: 0 AN: 28252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2742

European-Non Finnish (NFE) AF: 0.00000109 AC: 1 AN: 916146

Other (OTH) AF: 0.00 AC: 0 AN: 41386

GnomAD4 genome AF: 0.00000664 AC: 1 AN: 150526 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 73470

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

African (AFR) AF: 0.00 AC: 0 AN: 41264

American (AMR) AF: 0.00 AC: 0 AN: 15112

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3444

East Asian (EAS) AF: 0.00 AC: 0 AN: 5144

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9990

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67456

Other (OTH) AF: 0.000484 AC: 1 AN: 2068

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.060
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	4.9
DANN	Benign	0.92
DEOGEN2	Benign	0.016	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.37	T
M_CAP	Pathogenic	0.69	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.96	T
PhyloP100		0.079
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.48	N
REVEL	Benign	0.24
Sift	Benign	0.49	T
Sift4G	Benign	0.19	T
Polyphen		0.0	B
Vest4		0.098
MutPred		0.26		Gain of phosphorylation at P18 (P = 0.0059)
MVP		0.43
MPC		0.59
ClinPred		0.042	T
GERP RS		-3.9
PromoterAI		0.014	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		3.2
Varity_R		0.024
gMVP		0.17
Mutation Taster		=92/8	polymorphism

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: rs1001732920; hg19: chr17-43299543;