chr12-49684341-A-G

Position:

• chr12-49684341-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_175736.5(FMNL3):​c.127-15787T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 152,062 control chromosomes in the GnomAD database, including 5,857 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.22 (5857 hom., cov: 31)
• Consequence: FMNL3 NM_175736.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0890

Genes affected

FMNL3 (HGNC:23698): (formin like 3) The protein encoded by this gene contains a formin homology 2 domain and has high sequence identity to the mouse Wbp3 protein. Two alternative transcripts encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FMNL3	NM_175736.5	c.127-15787T>C		intron_variant		ENST00000335154.10	NP_783863.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FMNL3	ENST00000335154.10	c.127-15787T>C		intron_variant		1	NM_175736.5	ENSP00000335655
FMNL3	ENST00000352151.9	c.127-15787T>C		intron_variant		2		ENSP00000344311	P4
FMNL3	ENST00000550424.1	c.33+4104T>C		intron_variant		4		ENSP00000448939
FMNL3	ENST00000550488.5	c.127-15787T>C		intron_variant		5		ENSP00000447479	A1

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32720 AN: 151944 Hom.: 5815 Cov.: 31

Gnomad AFR AF: 0.498

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.0742

Gnomad SAS AF: 0.0988

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.191

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.216 AC: 32820 AN: 152062 Hom.: 5857 Cov.: 31 AF XY: 0.213 AC XY: 15812 AN XY: 74336

Gnomad4 AFR AF: 0.499

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.0739

Gnomad4 SAS AF: 0.0990

Gnomad4 FIN AF: 0.120

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.190

Alfa AF: 0.103 Hom.: 393

Bravo AF: 0.230

Asia WGS AF: 0.123 AC: 429 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	8.6
DANN	Benign	0.55

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: rs4133070; hg19: chr12-50078124;