dbSNP rs7978381: FMNL3:p.Tyr444Tyr (chr12-49652204-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_175736.5(FMNL3):c.1332T>C(p.Tyr444Tyr) 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.63

Publications

4 publications found

Variant links:

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]

FMNL3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
FMNL3	NM_175736.5 link	c.1332T>C	p.Tyr444Tyr	synonymous_variant	Exon 14 of 26	ENST00000335154.10	NP_783863.4	Q8IVF7-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FMNL3	ENST00000335154.10 link	c.1332T>C	p.Tyr444Tyr	synonymous_variant	Exon 14 of 26	1	NM_175736.5	ENSP00000335655.5	Q8IVF7-3
FMNL3	ENST00000550488.5 link	c.1332T>C	p.Tyr444Tyr	synonymous_variant	Exon 14 of 27	5		ENSP00000447479.1	F8W1F5
FMNL3	ENST00000352151.9 link	c.1179T>C	p.Tyr393Tyr	synonymous_variant	Exon 13 of 25	2		ENSP00000344311.5	Q8IVF7-2
FMNL3	ENST00000549137.1 link	n.39T>C		non_coding_transcript_exon_variant	Exon 1 of 13	5

Frequencies

GnomAD3 genomes

AF:

0.0146

AC:

2223

AN:

152152

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.00433

AC:

1059

AN:

244510

AF XY:

0.00372

show subpopulations

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 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.:

Cov.:

AF XY:

0.00177

AC XY:

1283

AN XY:

726150

show subpopulations

African (AFR)

AF:

0.0526

AC:

1761

AN:

33454

American (AMR)

AF:

0.00328

AC:

146

AN:

44544

Ashkenazi Jewish (ASJ)

AF:

0.000115

AC:

AN:

26054

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39668

South Asian (SAS)

AF:

0.00430

AC:

369

AN:

85742

European-Finnish (FIN)

AF:

0.0000753

AC:

AN:

53106

Middle Eastern (MID)

AF:

0.00434

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0000981

AC:

109

AN:

1111428

Other (OTH)

AF:

0.00404

AC:

244

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

162

324

485

647

809

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

116

174

232

290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0147

AC:

2239

AN:

152270

Hom.:

Cov.:

AF XY:

0.0147

AC XY:

1097

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.0504

AC:

2092

AN:

41544

American (AMR)

AF:

0.00608

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000386

AC:

AN:

5188

South Asian (SAS)

AF:

0.00373

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000162

AC:

AN:

68012

Other (OTH)

AF:

0.0104

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

196

294

392

490

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00551

Hom.:

Bravo

AF:

0.0168

Asia WGS

AF:

0.00866

AC:

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

(source)

DANN

Benign

0.17

PhyloP100

-1.6

Mutation Taster

=95/5

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over