NM_005248.3:c.1573C>T

Variant names:

• chr1-27612931-G-A
• rs143850913
• NM_005248.3:c.1573C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_005248.3(FGR):​c.1573C>T​(p.Pro525Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000234 in 1,613,986 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: 𝑓 0.00065 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00019 (0 hom.)
• Consequence: FGR NM_005248.3 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 9.94
• Publications: 4 publications found

Genes affected

FGR (HGNC:3697): (FGR proto-oncogene, Src family tyrosine kinase) This gene is a member of the Src family of protein tyrosine kinases (PTKs). The encoded protein contains N-terminal sites for myristylation and palmitylation, a PTK domain, and SH2 and SH3 domains which are involved in mediating protein-protein interactions with phosphotyrosine-containing and proline-rich motifs, respectively. The protein localizes to plasma membrane ruffles, and functions as a negative regulator of cell migration and adhesion triggered by the beta-2 integrin signal transduction pathway. Infection with Epstein-Barr virus results in the overexpression of this gene. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06930527).
• BS2: High AC in GnomAd4 at 99 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005248.3. 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
	FGR	NM_005248.3	MANE Select	c.1573C>T	p.Pro525Ser	missense	Exon 13 of 13	NP_005239.1	P09769
	FGR	NM_001042729.2		c.1573C>T	p.Pro525Ser	missense	Exon 13 of 13	NP_001036194.1	P09769
	FGR	NM_001042747.2		c.1573C>T	p.Pro525Ser	missense	Exon 13 of 13	NP_001036212.1	P09769

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGR	ENST00000374005.8	TSL:1 MANE Select	c.1573C>T	p.Pro525Ser	missense	Exon 13 of 13	ENSP00000363117.3	P09769
	FGR	ENST00000374004.5	TSL:1	c.1573C>T	p.Pro525Ser	missense	Exon 11 of 11	ENSP00000363116.1	P09769
	FGR	ENST00000968119.1		c.1588C>T	p.Pro530Ser	missense	Exon 13 of 13	ENSP00000638178.1

Frequencies

GnomAD3 genomes AF: 0.000650 AC: 99 AN: 152202 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00174

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000523

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000311 AC: 78 AN: 251026 AF XY: 0.000258

Gnomad AFR exome AF: 0.00148

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00162

Gnomad NFE exome AF: 0.0000969

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.000191 AC: 279 AN: 1461666 Hom.: 0 Cov.: 31 AF XY: 0.000180 AC XY: 131 AN XY: 727122

African (AFR) AF: 0.00146 AC: 49 AN: 33474

American (AMR) AF: 0.000134 AC: 6 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86214

European-Finnish (FIN) AF: 0.00118 AC: 63 AN: 53410

Middle Eastern (MID) AF: 0.000703 AC: 4 AN: 5690

European-Non Finnish (NFE) AF: 0.000123 AC: 137 AN: 1111956

Other (OTH) AF: 0.000331 AC: 20 AN: 60378

GnomAD4 genome AF: 0.000650 AC: 99 AN: 152320 Hom.: 0 Cov.: 32 AF XY: 0.000577 AC XY: 43 AN XY: 74488

African (AFR) AF: 0.00173 AC: 72 AN: 41564

American (AMR) AF: 0.000523 AC: 8 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.000471 AC: 5 AN: 10626

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

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68020

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.000294 Hom.: 0

Bravo AF: 0.000752

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000214 AC: 26

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Uncertain	-0.060
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.36	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Pathogenic	1.0	D
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.069	T
MetaSVM	Uncertain	-0.038	T
MutationAssessor	Benign	0.83	L
PhyloP100		9.9
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.41
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.014	D
Polyphen		0.99	D
Vest4		0.55
MVP		0.90
MPC		1.7
ClinPred		0.078	T
GERP RS		4.7
Varity_R		0.40
gMVP		0.48
Mutation Taster		=3/97	disease causing

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: rs143850913; hg19: chr1-27939442;