rs375291937

Variant names:

• chr19-49808445-A-G
• rs375291937
• NM_025129.5:c.1002T>C

Your query was ambiguous. Multiple possible variants found:

• chr19-49808445-A-G
• chr19-49808445-A-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_025129.5(FUZ):​c.1002T>C​(p.Tyr334Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000477 in 1,612,622 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00047 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00048 (1 hom.)
• Consequence: FUZ NM_025129.5 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0780
• Publications: 1 publications found

Genes affected

FUZ (HGNC:26219): (fuzzy planar cell polarity protein) This gene encodes a planar cell polarity protein that is involved in ciliogenesis and directional cell movement. Knockout studies in mice exhibit neural tube defects and defective cilia, and mutations in this gene are associated with neural tube defects in humans. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2012]

FUZ Gene-Disease associations (from GenCC):

• neural tube defects, susceptibility to

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 19-49808445-A-G is Benign according to our data. Variant chr19-49808445-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 769462.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.078 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025129.5. 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
	FUZ	NM_025129.5	MANE Select	c.1002T>C	p.Tyr334Tyr	synonymous	Exon 10 of 11	NP_079405.2
	FUZ	NM_001352262.2		c.1005T>C	p.Tyr335Tyr	synonymous	Exon 10 of 11	NP_001339191.1
	FUZ	NM_001171937.2		c.894T>C	p.Tyr298Tyr	synonymous	Exon 9 of 10	NP_001165408.1	Q9BT04-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FUZ	ENST00000313777.9	TSL:1 MANE Select	c.1002T>C	p.Tyr334Tyr	synonymous	Exon 10 of 11	ENSP00000313309.4	Q9BT04-1
	FUZ	ENST00000881282.1		c.1083T>C	p.Tyr361Tyr	synonymous	Exon 11 of 12	ENSP00000551341.1
	FUZ	ENST00000881283.1		c.1002T>C	p.Tyr334Tyr	synonymous	Exon 10 of 11	ENSP00000551342.1

Frequencies

GnomAD3 genomes AF: 0.000473 AC: 72 AN: 152140 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.000785

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000603

Gnomad OTH AF: 0.000958

GnomAD2 exomes AF: 0.000541 AC: 134 AN: 247544 AF XY: 0.000692

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000465

Gnomad ASJ exome AF: 0.000100

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000645

Gnomad OTH exome AF: 0.000661

GnomAD4 exome AF: 0.000477 AC: 697 AN: 1460364 Hom.: 1 Cov.: 32 AF XY: 0.000545 AC XY: 396 AN XY: 726426

African (AFR) AF: 0.000120 AC: 4 AN: 33470

American (AMR) AF: 0.000605 AC: 27 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.000115 AC: 3 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.00168 AC: 145 AN: 86100

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52724

Middle Eastern (MID) AF: 0.00457 AC: 26 AN: 5692

European-Non Finnish (NFE) AF: 0.000399 AC: 444 AN: 1111624

Other (OTH) AF: 0.000796 AC: 48 AN: 60314

GnomAD4 genome AF: 0.000473 AC: 72 AN: 152258 Hom.: 0 Cov.: 32 AF XY: 0.000470 AC XY: 35 AN XY: 74464

African (AFR) AF: 0.0000240 AC: 1 AN: 41582

American (AMR) AF: 0.000784 AC: 12 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00187 AC: 9 AN: 4824

European-Finnish (FIN) AF: 0.0000944 AC: 1 AN: 10590

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000603 AC: 41 AN: 67992

Other (OTH) AF: 0.000948 AC: 2 AN: 2110

Alfa AF: 0.000336 Hom.: 0

Bravo AF: 0.000446

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00115

EpiControl AF: 0.00136

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	8.0
DANN	Benign	0.65
PhyloP100		-0.078
PromoterAI		0.026	Neutral
Mutation Taster		=100/0	polymorphism

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: rs375291937; hg19: chr19-50311702;