rs7978381

Positions:

• chr12-49652204-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.1332T>C​(p.Tyr444=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00304 in 1,612,394 control chromosomes in the GnomAD database, including 121 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 0.015 (57 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (64 hom.)
• Consequence: FMNL3 NM_175736.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.63

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=-0.92).
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FMNL3	NM_175736.5	c.1332T>C	p.Tyr444=	synonymous_variant	14/26	ENST00000335154.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FMNL3	ENST00000335154.10	c.1332T>C	p.Tyr444=	synonymous_variant	14/26	1	NM_175736.5
FMNL3	ENST00000550488.5	c.1332T>C	p.Tyr444=	synonymous_variant	14/27	5		A1
FMNL3	ENST00000352151.9	c.1179T>C	p.Tyr393=	synonymous_variant	13/25	2		P4
FMNL3	ENST00000549137.1	n.39T>C		non_coding_transcript_exon_variant	1/13	5

Frequencies

GnomAD3 genomes AF: 0.0146 AC: 2223 AN: 152152 Hom.: 57 Cov.: 32

Gnomad AFR AF: 0.0501

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00609

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00373

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.0105

GnomAD3 exomes AF: 0.00433 AC: 1059 AN: 244510 Hom.: 16 AF XY: 0.00372 AC XY: 494 AN XY: 132832

Gnomad AFR exome AF: 0.0513

Gnomad AMR exome AF: 0.00319

Gnomad ASJ exome AF: 0.000202

Gnomad EAS exome AF: 0.000112

Gnomad SAS exome AF: 0.00457

Gnomad FIN exome AF: 0.0000472

Gnomad NFE exome AF: 0.000235

Gnomad OTH exome AF: 0.00422

GnomAD4 exome AF: 0.00182 AC: 2664 AN: 1460124 Hom.: 64 Cov.: 31 AF XY: 0.00177 AC XY: 1283 AN XY: 726150

Gnomad4 AFR exome AF: 0.0526

Gnomad4 AMR exome AF: 0.00328

Gnomad4 ASJ exome AF: 0.000115

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.00430

Gnomad4 FIN exome AF: 0.0000753

Gnomad4 NFE exome AF: 0.0000981

Gnomad4 OTH exome AF: 0.00404

GnomAD4 genome AF: 0.0147 AC: 2239 AN: 152270 Hom.: 57 Cov.: 32 AF XY: 0.0147 AC XY: 1097 AN XY: 74452

Gnomad4 AFR AF: 0.0504

Gnomad4 AMR AF: 0.00608

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00373

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.00390 Hom.: 13

Bravo AF: 0.0168

Asia WGS AF: 0.00866 AC: 30 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.018
DANN	Benign	0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs7978381; hg19: chr12-50045987;