6-41778251-A-T

Variant names:

• chr6-41778251-A-T
• rs3804281
• NM_006653.5:c.-167-75T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006653.5(FRS3):​c.-167-75T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FRS3 NM_006653.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.427
• Publications: 6 publications found

Genes affected

FRS3 (HGNC:16970): (fibroblast growth factor receptor substrate 3) This gene encodes a substrate for the fibroblast growth factor receptor. The encoded protein is found in the peripheral plasma membrane and links fibroblast growth factor receptor stimulation to activators of Ras. The encoded protein down-regulates extracellular regulated kinase 2 through direct binding. [provided by RefSeq, Jul 2013]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006653.5. 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
	FRS3	NM_006653.5	MANE Select	c.-167-75T>A		intron	N/A	NP_006644.1	O43559

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRS3	ENST00000373018.7	TSL:3 MANE Select	c.-167-75T>A		intron	N/A	ENSP00000362109.3	O43559
	FRS3	ENST00000930712.1		c.-167-75T>A		intron	N/A	ENSP00000600771.1
	FRS3	ENST00000930714.1		c.-162-75T>A		intron	N/A	ENSP00000600773.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 104 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 64

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 82

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 16

Other (OTH) AF: 0.00 AC: 0 AN: 6

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.0
DANN	Benign	0.85
PhyloP100		-0.43
PromoterAI		-0.014	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3804281; hg19: chr6-41745989;