rs7978381

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr12-49652204-A-G
• chr12-49652204-A-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.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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.63
• Publications: 4 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=-0.92).
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0506 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FMNL3	NM_175736.5	MANE Select	c.1332T>C	p.Tyr444Tyr	synonymous	Exon 14 of 26	NP_783863.4
	FMNL3	NM_001367835.1		c.1332T>C	p.Tyr444Tyr	synonymous	Exon 14 of 27	NP_001354764.1	Q8IVF7-1
	FMNL3	NM_198900.3		c.1179T>C	p.Tyr393Tyr	synonymous	Exon 13 of 25	NP_944489.2	Q8IVF7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FMNL3	ENST00000335154.10	TSL:1 MANE Select	c.1332T>C	p.Tyr444Tyr	synonymous	Exon 14 of 26	ENSP00000335655.5	Q8IVF7-3
	FMNL3	ENST00000865009.1		c.1392T>C	p.Tyr464Tyr	synonymous	Exon 15 of 27	ENSP00000535068.1
	FMNL3	ENST00000550488.5	TSL:5	c.1332T>C	p.Tyr444Tyr	synonymous	Exon 14 of 27	ENSP00000447479.1	F8W1F5

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

GnomAD2 exomes AF: 0.00433 AC: 1059 AN: 244510 AF XY: 0.00372

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.: 64 Cov.: 31 AF XY: 0.00177 AC XY: 1283 AN XY: 726150

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: 3 AN: 26054

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39668

South Asian (SAS) AF: 0.00430 AC: 369 AN: 85742

European-Finnish (FIN) AF: 0.0000753 AC: 4 AN: 53106

Middle Eastern (MID) AF: 0.00434 AC: 25 AN: 5764

European-Non Finnish (NFE) AF: 0.0000981 AC: 109 AN: 1111428

Other (OTH) AF: 0.00404 AC: 244 AN: 60364

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

African (AFR) AF: 0.0504 AC: 2092 AN: 41544

American (AMR) AF: 0.00608 AC: 93 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5188

South Asian (SAS) AF: 0.00373 AC: 18 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68012

Other (OTH) AF: 0.0104 AC: 22 AN: 2112

Alfa AF: 0.00551 Hom.: 19

Bravo AF: 0.0168

Asia WGS AF: 0.00866 AC: 30 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.018
DANN	Benign	0.17
PhyloP100		-1.6
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs7978381; hg19: chr12-50045987;