rs781102841

Variant names:

• chr17-45241583-A-C
• NM_005892.4:c.1534A>C

Your query was ambiguous. Multiple possible variants found:

• chr17-45241583-A-C
• chr17-45241583-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005892.4(FMNL1):​c.1534A>C​(p.Ser512Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000711 in 1,406,228 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. S512G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: FMNL1 NM_005892.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.218

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-AS1 (HGNC:55717): (FMNL1 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14197674).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FMNL1	NM_005892.4	c.1534A>C	p.Ser512Arg	missense_variant	Exon 14 of 27	ENST00000331495.8	NP_005883.3
FMNL1	NM_001411128.1	c.1534A>C	p.Ser512Arg	missense_variant	Exon 14 of 26		NP_001398057.1
FMNL1-AS1	NR_186807.1	n.188T>G		non_coding_transcript_exon_variant	Exon 1 of 2
FMNL1-AS1	NR_186808.1	n.188T>G		non_coding_transcript_exon_variant	Exon 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FMNL1	ENST00000331495.8	c.1534A>C	p.Ser512Arg	missense_variant	Exon 14 of 27	1	NM_005892.4	ENSP00000329219.2
FMNL1	ENST00000587489.6	c.1534A>C	p.Ser512Arg	missense_variant	Exon 14 of 26	1		ENSP00000465474.2
FMNL1-AS1	ENST00000587534.1	n.152T>G		non_coding_transcript_exon_variant	Exon 1 of 2	2
FMNL1	ENST00000587856.1	n.1891A>C		non_coding_transcript_exon_variant	Exon 7 of 16	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.11e-7 AC: 1 AN: 1406228 Hom.: 0 Cov.: 35 AF XY: 0.00000144 AC XY: 1 AN XY: 694400

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: 9.24e-7

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	0.19
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.033	T;T;.
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.72	T;T;T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-0.86	T
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.6	N;.;.
REVEL	Benign	0.15
Sift	Uncertain	0.019	D;.;.
Sift4G	Benign	0.53	T;T;T
Polyphen		0.61	P;.;.
Vest4		0.10
MutPred		0.35		Gain of solvent accessibility (P = 6e-04);.;.;
MVP		0.53
MPC		0.65
ClinPred		0.099	T
GERP RS		0.078
Varity_R		0.12
gMVP		0.21

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-43318950;