rs17123865

Positions:

• chr12-49672264-G-A
• chr12-49672264-G-C

Variant summary

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

The NM_175736.5(FMNL3):​c.127-3710C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0812 in 152,000 control chromosomes in the GnomAD database, including 533 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 0.081 (533 hom., cov: 32)
• Consequence: FMNL3 NM_175736.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.81

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0912 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FMNL3	NM_175736.5	c.127-3710C>T		intron_variant		ENST00000335154.10	NP_783863.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FMNL3	ENST00000335154.10	c.127-3710C>T		intron_variant		1	NM_175736.5	ENSP00000335655.5
FMNL3	ENST00000550488.5	c.127-3710C>T		intron_variant		5		ENSP00000447479.1
FMNL3	ENST00000352151.9	c.127-3710C>T		intron_variant		2		ENSP00000344311.5
FMNL3	ENST00000550424.1	c.34-3710C>T		intron_variant		4		ENSP00000448939.1

Frequencies

GnomAD3 genomes AF: 0.0812 AC: 12332 AN: 151882 Hom.: 532 Cov.: 32

Gnomad AFR AF: 0.0817

Gnomad AMI AF: 0.0659

Gnomad AMR AF: 0.0653

Gnomad ASJ AF: 0.0997

Gnomad EAS AF: 0.0275

Gnomad SAS AF: 0.0819

Gnomad FIN AF: 0.0442

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0932

Gnomad OTH AF: 0.0832

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

GnomAD4 genome AF: 0.0812 AC: 12345 AN: 152000 Hom.: 533 Cov.: 32 AF XY: 0.0783 AC XY: 5817 AN XY: 74296

Gnomad4 AFR AF: 0.0816

Gnomad4 AMR AF: 0.0651

Gnomad4 ASJ AF: 0.0997

Gnomad4 EAS AF: 0.0273

Gnomad4 SAS AF: 0.0824

Gnomad4 FIN AF: 0.0442

Gnomad4 NFE AF: 0.0931

Gnomad4 OTH AF: 0.0870

Alfa AF: 0.0758 Hom.: 229

Bravo AF: 0.0804

Asia WGS AF: 0.0800 AC: 278 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.5
DANN	Benign	0.57

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: rs17123865; hg19: chr12-50066047;