chr12-49672264-G-A

Variant names:

• chr12-49672264-G-A
• rs17123865
• NM_175736.5:c.127-3710C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175736.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FMNL3	NM_175736.5	MANE Select	c.127-3710C>T		intron	N/A	NP_783863.4
	FMNL3	NM_001367835.1		c.127-3710C>T		intron	N/A	NP_001354764.1
	FMNL3	NM_198900.3		c.127-3710C>T		intron	N/A	NP_944489.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FMNL3	ENST00000335154.10	TSL:1 MANE Select	c.127-3710C>T		intron	N/A	ENSP00000335655.5
	FMNL3	ENST00000550488.5	TSL:5	c.127-3710C>T		intron	N/A	ENSP00000447479.1
	FMNL3	ENST00000352151.9	TSL:2	c.127-3710C>T		intron	N/A	ENSP00000344311.5

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

African (AFR) AF: 0.0816 AC: 3383 AN: 41434

American (AMR) AF: 0.0651 AC: 995 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0997 AC: 346 AN: 3470

East Asian (EAS) AF: 0.0273 AC: 141 AN: 5156

South Asian (SAS) AF: 0.0824 AC: 396 AN: 4808

European-Finnish (FIN) AF: 0.0442 AC: 467 AN: 10554

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.0931 AC: 6332 AN: 67982

Other (OTH) AF: 0.0870 AC: 184 AN: 2114

Alfa AF: 0.0787 Hom.: 329

Bravo AF: 0.0804

Asia WGS AF: 0.0800 AC: 278 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.5
DANN	Benign	0.57
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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: rs17123865; hg19: chr12-50066047;