12-49652204-A-T

Variant names:

• chr12-49652204-A-T
• rs7978381
• NM_175736.5:c.1332T>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_175736.5(FMNL3):​c.1332T>A​(p.Tyr444*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FMNL3 NM_175736.5 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.63
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FMNL3	NM_175736.5	c.1332T>A	p.Tyr444*	stop_gained	Exon 14 of 26	ENST00000335154.10	NP_783863.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FMNL3	ENST00000335154.10	c.1332T>A	p.Tyr444*	stop_gained	Exon 14 of 26	1	NM_175736.5	ENSP00000335655.5
FMNL3	ENST00000550488.5	c.1332T>A	p.Tyr444*	stop_gained	Exon 14 of 27	5		ENSP00000447479.1
FMNL3	ENST00000352151.9	c.1179T>A	p.Tyr393*	stop_gained	Exon 13 of 25	2		ENSP00000344311.5
FMNL3	ENST00000549137.1	n.39T>A		non_coding_transcript_exon_variant	Exon 1 of 13	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.021	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	16
DANN	Benign	0.90
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.10	N
PhyloP100		-1.6
Vest4		0.85
GERP RS		-9.1
Mutation Taster		=11/189	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs7978381; hg19: chr12-50045987;