3-14922536-C-T

Variant names:

• chr3-14922536-C-T
• rs149798859
• NM_152536.4:c.3795C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BS1 BS2

The NM_152536.4(FGD5):​c.3795C>T​(p.His1265His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0207 in 1,581,348 control chromosomes in the GnomAD database, including 403 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 (29 hom., cov: 32)
  • Exomes 𝑓: 0.021 (374 hom.)
• Consequence: FGD5 NM_152536.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.73
• Publications: 1 publications found

Genes affected

FGD5 (HGNC:19117): (FYVE, RhoGEF and PH domain containing 5) Predicted to enable guanyl-nucleotide exchange factor activity and small GTPase binding activity. Predicted to be involved in several processes, including filopodium assembly; regulation of GTPase activity; and regulation of cell shape. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

LOC105376963 (HGNC:):

FGD5-AS1 (HGNC:40410): (FGD5 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP7: Synonymous conserved (PhyloP=-2.73 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0155 (2357/152252) while in subpopulation NFE AF = 0.0259 (1760/68022). AF 95% confidence interval is 0.0249. There are 29 homozygotes in GnomAd4. There are 1073 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 29 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152536.4. 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
	FGD5	NM_152536.4	MANE Select	c.3795C>T	p.His1265His	synonymous	Exon 15 of 20	NP_689749.3
	FGD5	NM_001320276.2		c.3795C>T	p.His1265His	synonymous	Exon 15 of 19	NP_001307205.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGD5	ENST00000285046.10	TSL:1 MANE Select	c.3795C>T	p.His1265His	synonymous	Exon 15 of 20	ENSP00000285046.5	Q6ZNL6-1
	FGD5	ENST00000543601.5	TSL:1	c.3072C>T	p.His1024His	synonymous	Exon 15 of 19	ENSP00000445949.1	B7ZM68
	FGD5	ENST00000476851.1	TSL:1	n.1332C>T		non_coding_transcript_exon	Exon 12 of 17

Frequencies

GnomAD3 genomes AF: 0.0155 AC: 2361 AN: 152134 Hom.: 30 Cov.: 32

Gnomad AFR AF: 0.00434

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00942

Gnomad ASJ AF: 0.0196

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00332

Gnomad FIN AF: 0.0156

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0259

Gnomad OTH AF: 0.0120

GnomAD2 exomes AF: 0.0160 AC: 3143 AN: 196662 AF XY: 0.0157

Gnomad AFR exome AF: 0.00454

Gnomad AMR exome AF: 0.00512

Gnomad ASJ exome AF: 0.0224

Gnomad EAS exome AF: 0.0000691

Gnomad FIN exome AF: 0.0171

Gnomad NFE exome AF: 0.0262

Gnomad OTH exome AF: 0.0126

GnomAD4 exome AF: 0.0213 AC: 30379 AN: 1429096 Hom.: 374 Cov.: 33 AF XY: 0.0208 AC XY: 14727 AN XY: 707610

African (AFR) AF: 0.00268 AC: 88 AN: 32876

American (AMR) AF: 0.00480 AC: 192 AN: 40020

Ashkenazi Jewish (ASJ) AF: 0.0193 AC: 493 AN: 25540

East Asian (EAS) AF: 0.0000788 AC: 3 AN: 38094

South Asian (SAS) AF: 0.00512 AC: 417 AN: 81466

European-Finnish (FIN) AF: 0.0178 AC: 897 AN: 50336

Middle Eastern (MID) AF: 0.00315 AC: 18 AN: 5718

European-Non Finnish (NFE) AF: 0.0250 AC: 27356 AN: 1095852

Other (OTH) AF: 0.0155 AC: 915 AN: 59194

GnomAD4 genome AF: 0.0155 AC: 2357 AN: 152252 Hom.: 29 Cov.: 32 AF XY: 0.0144 AC XY: 1073 AN XY: 74452

African (AFR) AF: 0.00433 AC: 180 AN: 41552

American (AMR) AF: 0.00941 AC: 144 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0196 AC: 68 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00332 AC: 16 AN: 4820

European-Finnish (FIN) AF: 0.0156 AC: 165 AN: 10594

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

European-Non Finnish (NFE) AF: 0.0259 AC: 1760 AN: 68022

Other (OTH) AF: 0.0109 AC: 23 AN: 2104

Alfa AF: 0.0207 Hom.: 15

Bravo AF: 0.0138

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.26
DANN	Benign	0.88
PhyloP100		-2.7
Mutation Taster		=99/1	polymorphism (auto)

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: rs149798859; hg19: chr3-14964043;